Inflammatory Cytokine Profile Research Articles

Abstract 265: Systemic Inflammation and Cardiac Macrophage Infiltration Accompany Stretch-induced Myocardial Injury in Swine Subjected to Transient Pressure Overload

Objective: Transient pressure overload (TPO) elicits stretch-induced myocyte injury in the absence of ischemia or infarction, but the extent to which this is associated with inflammation is unclear. The present study was designed to assess immune activation after TPO in swine and compare the inflammatory cytokine profile to that observed after myocardial infarction (MI). Methods: Swine received a brief infusion of phenylephrine (18 mg/hr iv; 30-60 min) to induce TPO and were studied for 1 hr (n=5), 3 hr (n=6), or 24 hr (n=6) before analysis of myocardial macrophage gene expression (CD68) via qPCR. Serial blood sampling was performed to assess neutrophil and monocyte counts as well as circulating cardiac troponin I (cTnI), IL-6, TNF-α, and CRP. Cytokine levels were compared to those from a separate group (n=5) subjected to a 60 min LAD occlusion to produce MI. Results: TPO increased circulating cTnI (from 20±5 ng/L to 340±58 ng/L at 3 hr and 1520±616 ng/L at 24 hr; p<0.01) without evidence of infarction. Compared with controls (n=6), swine subjected to TPO exhibited increased CD68 gene expression at 1, 3, and 24 hr ( A ). This was accompanied by a rise in peripheral blood neutrophils and monocytes ( B ) as well as an elevation in circulating IL-6, TNF-α, and CRP that was comparable to that observed after MI ( C ). Conclusion: Myocyte injury following TPO elicits mobilization of neutrophils and monocytes and a rise in circulating inflammatory cytokines comparable to that observed after MI. This is accompanied by an increase in cardiac macrophages and may be an important mechanism by which repetitive episodes of TPO lead to interstitial fibrosis and diastolic dysfunction without anatomic hypertrophy.

Profiling ocular surface responses to preserved and non-preserved topical glaucoma medications: A 2-year randomized evaluation study.

Use of topical glaucoma medications has been reported to cause ocular surface (OS) discomfort and inflammation. This study explores the profile of inflammatory cytokines and OS symptoms induced in response to preserved and non-preserved drops. Prospective, randomized evaluation on 36 treatment-naïve patients over 24 months of three differently preserved glaucoma drop preparations: Preservative-free (PF), polyquad (PQ) and benzalkonium chloride (BAK). Study participants were evaluated at baseline and then at 1, 3, 6, 12 and 24 months while on medication. At each visit, participants completed the OS disease index (OSDI) questionnaire, had basal tear sampling and impression cytology (IC) of the conjunctival epithelium. Quantitative polymerase chain reaction was performed to measure the gene expression of inflammatory cytokines [interleukin (IL)-6, IL-8, IL-10, IL-12A, IL-12B, IL-17A, IL-1β and tumour necrosis factor-α] in the IC samples. Corresponding protein expression of cytokines in tear samples was assessed by the Becton-Dickinson cytometric bead arrays. Compared to PF and PQ groups, mRNA and protein expression of IL-6, IL-8 and IL-1β increased in samples from the BAK group in a time-dependent fashion, whereas all other cytokines showed a non-significant increase. In the BAK group, there was a strong correlation between OSDI and the levels of IC/IL-1β (r = .832, R2 = .692 and P = .040); IC/IL-10 (r = .925, R2 = .856 and P = .008) and tear/IL-1β (r = .899, R2 = .808 and P = .014). BAK-preserved topical drops stimulate a sterile inflammatory response on the OS within 3 months which is maintained thereafter, whereas PF-drops and PQ-preserved drops showed no significant OS inflammation.

Aberrations in peripheral inflammatory cytokine levels in substance use disorders: a meta-analysis of 74 studies.

To characterize the peripheral inflammatory cytokine profile in people with substance use disorders (SUDs). Systematic review and meta-analysis. Clinical studies that evaluated peripheral blood inflammatory cytokine levels in patients with SUDs and healthy controls PARTICIPANTS: SUD patients and healthy controls. PubMed and Web of Science were systematically searched for relevant studies. Two investigators independently selected studies and extracted data. A total of 77 articles were included in the meta-analysis, containing 5649 patients with SUDs and 4643 healthy controls. Data were pooled using a random-effects model by the Comprehensive Meta-Analysis version 2 software. Concentrations of interleukin (IL)-6) in 32 studies, tumor necrosis factor (TNF)-α in 28 studies, IL-10 in 20 studies, IL-8 in 17 studies, C-reactive protein in 14 studies, IL-4 in 10 studies, IL-12 in seven studies, monocyte chemoattractant protein (MCP)-1 in 6 studies, TNF-receptor 2 (TNF-R2) in four studies and granulocyte-macrophage colony-stimulating factor (GM-CSF) in three studies were significantly higher in patients with SUDs compared with healthy controls, while concentrations of leptin in 14 studies were significantly lower in patients with SUDs compared with healthy controls. The findings were inconclusive for the associations between interferon-γ, IL-1β, IL-2, IL-1 receptor antagonist (IL-1RA), transforming growth factor (TGF)-β1, G-CSF, C-C motif chemokine 11, TGF-α and SUDs. People with substance use disorders (SUDs) appear to have higher peripheral concentrations of IL-4, IL-6, IL-8, IL-10, IL-12, TNF-α, C-reactive protein, MCP-1, TNF-R2 and GM-CSF and lower peripheral concentrations of leptin than people without SUDs. This strengthens the view that SUD is accompanied by an inflammatory response.

Enhanced local and systemic inflammatory cytokine mRNA expression in women with endometriosis evokes compensatory adaptive regulatory mRNA response that mediates immune suppression and impairs cytotoxicity.

Endometriosis is a disease characterized by ectopic implantation of endometrium and impaired immune responses. To explore its pathogenic mechanisms, we studied the local and systemic cytokine mRNA profiles and their role in the immunity of patients with endometriosis and healthy controls. mRNA for eleven cytokines defining cytotoxic Th1, humoral Th2, regulatory Tr1/Th3, and inflammatory cytokine profiles was characterized locally in endometriotic tissue and endometrium, and systemically in PBMCs from women with endometriosis and healthy controls, using real-time qRT-PCR. In addition, immunohistochemical stainings with monoclonal antibodies were performed looking for T regulatory cells in endometriotic lesions. We found a downregulation of mRNA for cytokines mediating cytotoxicity and antibody response and an upregulation of inflammatory and T-regulatory cytokines in the endometriotic tissues and endometrium from the patients with endometriosis, suggesting enhanced local inflammation and priming of an adaptive regulatory response. Consistent with those findings, there was an abundancy of T regulatory cells in the endometriotic lesions. The ectopic implantation seen in endometriosis could be possible as a consequence of increased inflammation and priming of adaptive T regulatory cells, resulting in impaired cytotoxicity and enhanced immune suppression.

Expression Profiles of Inflammatory Cytokines in the Aqueous Humor of Children after Congenital Cataract Extraction.

PurposeTo investigate the change in cytokine microenvironment of the aqueous humor (AH) after surgery in children with congenital or developmental cataracts.MethodsAH samples were obtained from 59 eyes diagnosed with a congenital or developmental cataract. Thirty-three of these eyes were aphakic following previous cataract surgery and were scheduled for secondary intraocular lens (IOL) implantation. Additionally, AH samples from 26 eyes that had not undergone surgery were taken. AH samples were then analyzed for 16 different inflammatory immune mediators using multiplex bead immunoassays and enzyme-linked immunosorbent assay (ELISA).ResultsThe mean interval between secondary IOL implantation and original cataract surgery was 24.85 months (range, 9–60 months). Levels of IL-6, IP-10 (CXCL10), MCP-1 (CCL2), and IL-2 were significantly elevated in the AH of eyes after surgery compared to eyes that did not undergo surgery (P < 0.001, P = 0.047, P = 0.006, P = 0.012, respectively). There was significant correlation between the levels of TGF-β2 and intraocular pressure (IOP) in postsurgical and nonsurgical eyes (r = 0.532, P = 0.006; r = 0.57, P = 0.001). Postsurgical outcomes, such as iris adhesions, capsular fibrosis, and capsular contraction, were found not to be significantly associated with cytokine levels in the AH after surgery; however, IL-6 levels in capsular exposure eyes were significantly higher than those in cortical closure eyes (P = 0.023).ConclusionsTo our knowledge, this is the first study to report significantly increased proinflammatory cytokine levels in the AH after congenital cataract extraction in children. Our study also suggests that this proinflammatory state may be maintained for a prolonged period of time. Overall, these results give us insight into the relationship between the inflammatory cytokine microenvironment of the aqueous humor and potential long-term complications following congenital cataract surgery.Translational RelevanceThe inflammatory cytokine microenvironment of the aqueous humor might help explain potential long-term complications after surgery in patients with congenital or developmental cataracts.

Early versus Late Profiles of Inflammatory Cytokines after Mild Traumatic Brain Injury and Their Association with Neuropsychological Outcomes.

Despite pre-clinical evidence for the role of inflammation in traumatic brain injury (TBI), there is limited data on inflammatory biomarkers in mild TBI (mTBI). In this study, we describe the profile of plasma inflammatory cytokines and explore associations between these cytokines and neuropsychological outcomes after mTBI. Patients with mTBI with negative computed tomography and orthopedic injury (OI) controls without mTBI were prospectively recruited from emergency rooms at three trauma centers. Plasma inflammatory cytokine levels were measured from venous whole-blood samples that were collected at enrollment (within 24 h of injury) and at 6 months after injury. Neuropsychological tests were performed at 1 week, 1 month, 3 months, and 6 months after the injury. Multivariate regression analysis was performed to identify associations between inflammatory cytokines and neuropsychological outcomes. A total of 53 mTBI and 24 OI controls were included in this study. The majority of patients were male (62.3%), and injured in motor vehicle accidents (37.7%). Plasma interleukin (IL)-2 (p = 0.01) and IL-6 (p = 0.01) within 24 h post-injury were significantly higher for mTBI patients compared with OI controls. Elevated plasma IL-2 at 24 h was associated with more severe 1-week post-concussive symptoms (p = 0.001). At 6 months, elevated plasma IL-10 was associated with greater depression scores (p = 0.004) and more severe post-traumatic stress disorder (PTSD) symptoms (p = 0.001). Plasma cytokine levels (within 24 h and at 6 months post-injury) were significantly associated with early and late post-concussive symptoms, PTSD, and depression scores after mTBI. These results highlight the potential role of inflammation in the pathophysiology of post-traumatic symptoms after mTBI.

Design and rationale of a nationwide screening analysis from the LIPIDOGRAM2015 and LIPIDOGEN2015 studies

IntroductionCardiovascular disease (CVD) is a major cause of morbidity and mortality throughout the world. The LIPIDOGRAM2015 study was performed to estimate the prevalence of risk factors for atherosclerotic diseases as well as cardiovascular and related disorders in the primary care setting in Poland. The LIPIDOGEN2015 sub-study was designed to include a random cohort of patients in order to analyse parameters related to lipid metabolism, oxidative stress, inflammatory responses, autoimmune disorders, and gene variants that confer susceptibility to cardiometabolic and atherosclerotic diseases.Material and methodsThe recruitment was carried out by 438 primary care physicians in Poland. The expected number of patients recruited for the LIPIDOGRAM2015 study was 13,000–14,000 with 13–15% (1700–2000) also participating in the LIPIDOGEN2015 sub-study. Each patient had to complete a questionnaire concerning medical and family history, concomitant diseases, and pharmacotherapy. Anthropometric measurements were performed at the doctor’s office. For the LIPIDOGEN2015 sub-study, saliva samples for DNA isolation and blood samples for measurement of glycated haemoglobin, oxidative stress parameters, autoantibody levels, and inflammatory cytokine profile and apolipoprotein profile were collected. Follow-up data will be obtained from the National Health Fund in Poland.ResultsThe LIPIDOGRAM2015 and LIPIDOGEN2015 study cohort reflects the prevalence of cardiovascular risk factors and concomitant diseases, markers of oxidative stress, the presence of autoantibodies, inflammatory cytokine profile, and apolipoprotein profile, as well as genetic variants potentially conferring susceptibility to cardiometabolic and atherosclerotic diseases.ConclusionsThis study presents the prevalence of different CV risk factors, with special emphasis on lipid disorders, and it assesses the relationship between inflammation, oxidative stress, and mutations in genes encoding proteins regulating lipid metabolism, as well as genes conferring susceptibility to cardiovascular, cardiometabolic, and related diseases.

Thalidomide combined with low-dose short-term glucocorticoid in the treatment of critical Coronavirus Disease 2019.

Thalidomide combined with low-dose short-term glucocorticoid in the treatment of critical Coronavirus Disease 2019.

Correlation between elevated inflammatory cytokines of spleen and spleen index in acute spinal cord injury

BackgroundSpinal cord injury (SCI) is a devastating disorder. After SCI, it initiates a robust immune response. Considering the spleen is one of the most important immune organs, the present study further characterizes the inflammatory cytokine profile of spleen in acute SCI. MethodsAdult rats were divided into sham and SCI groups (n = 36). SCI was produced at the T3 vertebral level. The whole blood and spleen was collected at 6, 24, 48, 72, 120, and 168 h after SCI. The levels of the inflammatory factors (IL-1β, IL-6, IL-10, TNF-α, and TGF-β) in spleen and serum were measured with an ELISA kit. ResultsThe results showed significantly elevated levels of IL-1β, IL-6, IL-10 and TNF-α in spleen compared with control group levels. Inflammatory cytokine levels of spleen correlated negatively with spleen index. ConclusionIt was found that inflammatory cytokines in spleen showed dynamic responses to SCI, which suggest their specificity change of spleen caused by SCI. These results suggest that a possible involvement of spleen in the initiation of the inflammatory response after SCI.

Anti-Aminoacyl Transfer-RNA-Synthetases (Anti-tRNA) Autoantibodies Associated with Interstitial Lung Disease: Pulmonary Disease Progression has a Persistent Elevation of the Th17 Cytokine Profile.

Anti-tRNA autoantibodies are associated with interstitial lung disease (ILD), in at least two clinical scenarios: the anti-synthetase syndrome (ASSD) and interstitial pneumonia with autoimmune features (IPAF). Under pathological conditions, cytokines indicate the participating elements and the course of inflammatory phenomena. We aimed to quantify serum concentrations of different inflammatory cytokines profiles in patients with anti-tRNA associated ILD (anti-tRNA-ILD) and estimate the association between these and ILD improvement and progression. Serum levels of 18 cytokines from baseline and after six months of treatment of ILD patients’ positives to anti-tRNA were included in the current study. At six months, patients were classified as with or without ILD progression. A total of 39 patients were included (10 anti-Jo1, eight anti-PL7, 11 anti-PL12, and 10 anti-Ej). Three patients (7.6%) had ILD progression (progressors patients, PP) and showed statistically higher levels in IL-4, IL-10, IL-17A, IL-22, GM-CSF, IL-1β, IL-6, IL-12, IL-18, and TNF-α, compared to patients without disease progression (no progressors patients, NPP). IL-17A, IL-1β, and IL-6 (T-helper-lymphocyte (Th)17 inflammatory cytokine profile) were elevated and had a high discriminatory capacity in distinguishing ILD PP of those NPP at follow-up. Overall, there is an association between the cytokines of the Th17 inflammatory profile and the ASSD progression.

Acute Phase Proteins, Trace Elements and Cytokines Expression as A Diagnostic and Prognostic Biomarker in Diseased Camel

The present study was carried out to evaluate the diagnostic value of inflammatory biomarkers on diseased camels via exploring the possible effects on oxidants and antioxidants status in addition to characterizing the profiles of acute phase proteins and inflammatory cytokines. Forty-eight adult male and female dromedary camels (Camelus dromedaries) were examined, according to general health conditions, clinical and laboratory diagnosis they were split into 3 groups. Group 1: Included 20 apparently healthy camels act as a control group, Group 2: Included 12 camels suffered from trypanosomiasis, Group 3: Included 16 camels suffered from mange. Our results revealed that the mean values of copper and zinc were significantly decreased with statistical elevation of MDA and statistical lowering of catalase and total antioxidant capacity in cases of trypanosomiasis and mange compared to apparently clinically healthy camels (P value <0.05), there is a pearson negative correlation between copper and MDA (r=-0.6; P<0.05) in diseased camels, The mean values of acute phase proteins (haptoglobin, ceruloplasmin and serum amyloid A) and inflammatory cytokines (IL-1, IL-6, IL-10 and TNF-α) were significantly elevated in diseased camels at (Trypanosomiasis and mange) than apparently clinically healthy camels (P value <0.05).

Activation of the Intracellular Pattern Recognition Receptor NOD2 Promotes Acute Myeloid Leukemia (AML) Cell Apoptosis and Provides a Survival Advantage in an Animal Model of AML.

TLRs, a family of membrane-bound pattern recognition receptors found on innate immune cells, have been well studied in the context of cancer therapy. Activation of these receptors has been shown to induce inflammatory anticancer events, including differentiation and apoptosis, across a wide variety of malignancies. In contrast, intracellular pattern recognition receptors such as NOD-like receptors have been minimally studied. NOD2 is a member of the NOD-like receptor family that initiates inflammatory signaling in response to the bacterial motif muramyl dipeptide. In this study, we examined the influence of NOD2 in human acute myeloid leukemia (AML) cells, demonstrating that IFN-γ treatment upregulated the expression of NOD2 signaling pathway members SLC15A3 and SLC15A4, downstream signaling kinase RIPK2, and the NOD2 receptor itself. This priming allowed for effective induction of caspase-1-dependent cell death upon treatment with muramyl tripeptide phosphatidylethanolamine (MTP-PE), a synthetic ligand for NOD2. Furthermore, the combination of MTP-PE and IFN-γ on AML blasts generated an inflammatory cytokine profile and activated NK cells. In a murine model of AML, dual treatment with MTP-PE and IFN-γ led to a significant increase in mature CD27- CD11b+ NK cells as well as a significant reduction in disease burden and extended survival. These results suggest that NOD2 activation, primed by IFN-γ, may provide a novel therapeutic option for AML.

Lesional Inflammatory Profile in Hidradenitis Suppurativa Is Not Solely Driven by IL-1

Lesional Inflammatory Profile in Hidradenitis Suppurativa Is Not Solely Driven by IL-1

Long-term Impact of Mini-Gastric Bypass on Inflammatory Cytokines in Cohort of Morbidly Obese Patients: a Prospective Study.

One anastomosis gastric bypass (OAGB) is a promising bariatric procedure. We performed this study to evaluate the changes in a group of inflammatory cytokines 12months after OAGB. A single-arm prospective study was conducted on obese patients who underwent OAGB. The serum levels of the following adipocytokines were monitored pre- and 12months postoperatively: adiponectin, leptin, interleukin 6 (IL-6), interleukin 8 (IL-8) levels, tumor necrosis factor-alpha (TNF-α), serum amyloid A (SAA), high-sensitivity C-reactive protein (hs-CRP), and monocyte chemotactic protein 1 (MCP-1). A total of 62 patients were included with a mean age of 43.9 ± 6.8years old. The serum adiponectin increased significantly from 7.64 ± 0.29 to 8.76 ± 0.42μg/mL 12months after the operation (p < 0.001). hs-CRP and IL-6 decreased significantly 12months after the OAGB from 3323.35 ± 643.4ng/mL and 3.72 ± 7.7pg/mL to 1376.81 ± 609.4ng/mL and 3.64 ± 6.9pg/mL, respectively (p < 0.001). The MCP-1 showed significant increase in its level after OAGB as well (p = 0.014). In contrary, there were no significant changes in serum levels of IL-8 (p = 0.12) and TNF-α (p = 0.84) 12months after the operation. The correlation analysis showed significant correlations between initial body mass index (BMI) with serum adiponectin, IL-8, and serum SAA. OAGB can significantly impact the inflammatory cytokine profile in obese patients with possible subsequent protection from obesity-related comorbidities such as insulin resistance, cardiovascular diseases, and certain cancers.

Low Molecular Weight Hyaluronan Induces an Inflammatory Response in Ovarian Stromal Cells and Impairs Gamete Development In Vitro.

The ovarian stroma, the microenvironment in which female gametes grow and mature, becomes inflamed and fibrotic with age. Hyaluronan is a major component of the ovarian extracellular matrix (ECM), and in other aging tissues, accumulation of low molecular weight (LMW) hyaluronan fragments can drive inflammation. Thus, we hypothesized that LMW hyaluronan fragments contribute to female reproductive aging by stimulating an inflammatory response in the ovarian stroma and impairing gamete quality. To test this hypothesis, isolated mouse ovarian stromal cells or secondary stage ovarian follicles were treated with physiologically relevant (10 or 100 μg/mL) concentrations of 200 kDa LMW hyaluronan. In ovarian stromal cells, acute LMW hyaluronan exposure, at both doses, resulted in the secretion of a predominantly type 2 (Th2) inflammatory cytokine profile as revealed by a cytokine antibody array of conditioned media. Additional qPCR analyses of ovarian stromal cells demonstrated a notable up-regulation of the eotaxin receptor Ccr3 and activation of genes involved in eosinophil recruitment through the IL5-CCR3 signaling pathway. These findings were consistent with an age-dependent increase in ovarian stromal expression of Ccl11, a major CCR3 ligand. When ovarian follicles were cultured in 10 or 100 μg/mL LMW hyaluronan for 12 days, gametes with compromised morphology and impaired meiotic competence were produced. In the 100 μg/mL condition, LMW hyaluronan induced premature meiotic resumption, ultimately leading to in vitro aging of the resulting eggs. Further, follicles cultured in this LMW hyaluronan concentration produced significantly less estradiol, suggesting compromised granulosa cell function. Taken together, these data demonstrate that bioactive LMW hyaluronan fragments may contribute to reproductive aging by driving an inflammatory stromal milieu, potentially through eosinophils, and by directly compromising gamete quality through impaired granulosa cell function.

ASIC1a induces synovial inflammation via the Ca2+/NFATc3/ RANTES pathway.

Rationale: Synovial inflammation is one of the main pathological features of rheumatoid arthritis (RA) and is a key factor leading to the progression of RA. Understanding the regulatory mechanism of synovial inflammation is crucial for the treatment of RA. Acid-sensing ion channel 1a (ASIC1a) is an H+-gated cation channel that promotes the progression of RA, but the role of ASIC1a in synovial inflammation is unclear. This study aimed to investigate whether ASIC1a is involved in the synovial inflammation and explore the underlying mechanisms in vitro and in vivo.Methods: The expression of ASIC1a and nuclear factor of activated T cells (NFATs) were analyzed by Western blotting, immunofluorescence, and immunohistochemistry both in vitro and in vivo. The Ca2+ influx mediated by ASIC1a was detected by calcium imaging and flow cytometry. The role of ASIC1a in inflammation was studied in rats with adjuvant-induced arthritis (AA). Inflammatory cytokine profile was analyzed by protein chip in RA synovial fibroblasts (RASF) and verified by a magnetic multi-cytokine assay and ELISA. The NFATc3-regulated RANTES (Regulated upon activation, normal T cell expressed and secreted) gene transcription was investigated by ChIP-qPCR and dual-luciferase reporter assay.Results: The expression of ASIC1a was significantly increased in human RA synovial tissues and primary human RASF as well as in ankle synovium of AA rats. Activated ASIC1a mediated Ca2+ influx to increase [Ca2+]i in RASF. The activation/overexpression of ASIC1a in RASF up-regulated the expression of inflammatory cytokines RANTES, sTNF RI, MIP-1a, IL-8, sTNF RII, and ICAM-1 among which RANTES was increased most remarkably. In vivo, ASIC1a promoted inflammation, synovial hyperplasia, articular cartilage, and bone destruction, leading to the progression of AA. Furthermore, activation of ASIC1a upregulated the nuclear translocation of NFATc3, which bound to RANTES promoter and directly regulated gene transcription to enhance RANTES expression.Conclusion: ASIC1a induces synovial inflammation, which leads to the progression of RA. Our study reveals a novel RA inflammation regulatory mechanism and indicates that ASIC1a might be a potential therapeutic target for RA.

Mycobacterial Phthiocerol Dimycocerosate Induces Galectin-3 Upregulation to Impair Proinflammatory Responses and Favor Immune Evasion in vivo

Mycobacterium tuberculosis (Mtb), a typical intracellular parasite that cause tuberculosis (TB), which rank the top infectious killer for human death. Pathogenic mycobacterium has evolved numerous strategies to favor their intracellular survival including a unique lipid-rich cell wall component and granuloma formation during early infection [1]. Phthiocerol dimycocerosate (PDIM) is a critical virulence factor of mycobacteria including Mycobacterium marinum (Mm), which manipulate host immune responses and granuloma induction and facilitate immune evasion [2-7], but the mechanisms are still remains questionable. We used an AACT/SILAC-based quantitative proteomic approach to determine PDIM-responded proteome profiles during Mm early infection. A major difference was the high abundance of galectin3 (Gal-3) in WT Mm-infected cells and not with PDIM-deficient. Gal-3 induction by PDIM-replete bacteria was primarily via Toll-like receptor 2, and also engaged TGF-β non-classical pathway. Elevated Gal-3 in macrophages prevented the turnover and translocation of NF-κB to effectively modulate the profile of inflammatory cytokines. Silencing of Gal-3 effectively relieved tissue damage induced in mice by PDIM-expressing Mm. We found upregulated Gal-3 in the serum and BALF of confirmed clinical tuberculosis cases, while decreased significantly after effective chemotherapy. Our findings demonstrated that upregulated Gal-3 not only plays an important role in regulating host immune response and granuloma formation in vivo, but also that target-Gal-3 therapy is a promising anti-tuberculosis strategy in the future. Funding Statement: This work was supported in part by the National Natural Science Foundation of China (Grant Nos. 31772709 and 31572485 to D.W), the new faculty startup research fund of China Three Gorges University (KJ2014B023 to D.W), Health Commission of Hubei Province in China (WJ2019H528 to D.W; WJ2019F080 to D.L), and in part by the intramural research program of NIAID, NIH (Bethesda MD, USA). Z.L was supported by grants from the China’s 13th Five Year Programs for the prevention and cure of great infectious diseases (2017ZX10201301-005) and Open Fund of Shanghai Key Laboratory of Tuberculosis (2018kf03). XY.Fan is the recipient of National Natural Science Foundation of China (31771004). Declaration of Interests: The authors declare no competing financial interests. Ethics Approval Statement: The case-control study of TB was reviewed and approved by the Ethics Committee of the Third People’s Hospital of Yichang (2017008H). Written informed consent was obtained from all participants. The animal experiments were reviewed and approved by the Animal Care and Use Committee of China Three Gorges University (2017010M).

Inflammation: A protagonist in development of carcinogen induced cervical cancer in mice

Inflammation- induced systemic stress plays an essential role in neoplastic progression. Chronic exposure to chemical carcinogens can induce persistent inflammatory changes which further augment loss in physiological hormesis of an organism thereby favouring carcinogenesis. The present study investigated the role of inflammation and associated systemic stress in the development of cervical carcinoma in a 3-methylcholanthrene (3-MC; a chemical carcinogen) induced in vivo cervical cancer model. When the cervix of 5-6 weeks old virgin female Swiss Albino mice (Mus musculus) was treated with 3-MC (0.6 mg/mL), remarkable alteration in its cervical cytopathology was observed. An increase in duration of 3-MC treatment caused an outburst in the number and variety of infiltrating granulocytes and agranulocytes in mice cervix. Thus, a high leukocyte index was indicative of prevalent cervical inflammatory changes. Elevated activities of SGPT, SGOT, serum alkaline phosphatase enzymes along with the presence of elevated serum creatinine levels suggested liver and renal dysfunctions. These observations were supported by alterations in hepatic histopathology of 3-MC treated mice. Surged activities and expression profiles of inflammatory cytokines (IL-6 and IL-8) in cervix tissue had conclusively established the crucial role played by inflammation- mediated systemic stress in favouring the development of cervical cancer in a carcinogen-induced in vivo model.

Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients

ABSTRACT Circulating in China and 158 other countries and areas, the ongoing COVID-19 outbreak has caused devastating mortality and posed a great threat to public health. However, efforts to identify effectively supportive therapeutic drugs and treatments has been hampered by our limited understanding of host immune response for this fatal disease. To characterize the transcriptional signatures of host inflammatory response to SARS-CoV-2 (HCoV-19) infection, we carried out transcriptome sequencing of the RNAs isolated from the bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) specimens of COVID-19 patients. Our results reveal distinct host inflammatory cytokine profiles to SARS-CoV-2 infection in patients, and highlight the association between COVID-19 pathogenesis and excessive cytokine release such as CCL2/MCP-1, CXCL10/IP-10, CCL3/MIP-1A, and CCL4/MIP1B. Furthermore, SARS-CoV-2 induced activation of apoptosis and P53 signalling pathway in lymphocytes may be the cause of patients’ lymphopenia. The transcriptome dataset of COVID-19 patients would be a valuable resource for clinical guidance on anti-inflammatory medication and understanding the molecular mechansims of host response.

Transcriptomic Characteristics of Bronchoalveolar Lavage Fluid and Peripheral Blood Mononuclear Cells in COVID-19 Patients

Circulating in China and 75 other countries and territories, the ongoing COVID-19 outbreak has caused devastating mortality and posed a great threat to public health. However, efforts to identify effectively supportive therapeutic drugs and treatments has been hampered by our limited understanding of host immune response for this fatal disease. To characterize the transcriptional signatures of host inflammatory response to SARS-CoV-2 infection, we carried out transcriptome sequencing of the RNAs isolated from the bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) specimens of COVID-19 patients. Our results reveal distinct host inflammatory cytokine profiles to SARS-CoV-2 infection in patients, and highlight the association between COVID-19 pathogenesis and excessive cytokine release such as CCL2/MCP-1, CXCL10/IP-10, CCL3/MIP-1A, and CCL4/MIP1B. Furthermore, SARS-CoV-2 induced activation of apoptosis and P53 signaling pathway in lymphocytes may be the cause of patients’ lymphopenia. The transcriptome dataset of COVID-19 patients would be a valuable resource for clinical guidance on anti-inflammatory medication and understanding the molecular mechansims of host response. Funding: This study was supported by Special Fund for COVID-19 Research of Wuhan University, National Science and Technology Major Project (#2018ZX10733403), China NSFC grants (#81672008, 31871316), Hubei Natural Science Foundation (#2018CFA035), Basic Scientific Research Foundation of Central Universities (#2042019gf0026), Ministry of Science and Technology of China, the National Mega Project on Major Infectious Disease Prevention (#2017ZX10103005) and National Key Research and Development Program of China (#2018YFE0204500). Declaration of Interest: The authors declare no competing interests. Ethical Approval: This study was approved by the Ethics Committee of the Zhongnan Hospital of Wuhan University. The RNA-seq analyses of BALF samples and PBMC were performed on existing samples collected during standard diagnostic tests, posing no extra burden to patients.