hBD-2 Levels Research Articles

Association of human beta-defensin 1 gene polymorphisms with nonsegmental vitiligo.

Vitiligo is a pigmentation disorder of autoimmune aetiology. Polymorphisms in beta-defensin genes have been linked to a predisposition to some autoimmune disorders. To evaluate the role of polymorphisms in DEFB1, the gene encoding for human beta-defensin (HBD)-1 and its 5' untranslated region in nonsegmental vitiligo. In total, 354 participants [171 patients with non-segmental vitiligo and 183 age and sex-matched healthy controls (HCs)], were genotyped by the PCR-restriction fragment length polymorphism (RFLP) method. For 80 of these individuals (40 patients and -40 HCs) serum HBD-1 was also measured by ELISA. The -44G allele, CG genotype and GGG haplotype increased the risk for vitiligo (P<0.02 in all cases), whereas the -20 AA genotype seems to be protective (P=0.04). Serum HBD-1 levels were lower in patients with vitiligo than in HCs (P<0.01), as well as in patients with active vitiligo compared with those with stable vitiligo and with HCs (P<0.05 in both cases), CONCLUSION: Our results suggest that HBD-1 and its gene polymorphisms may modulate vitiligo susceptibility and/or disease activity. This is the first report, to our knowledge, of the association of serum HBD-1 levels and DEFB1 gene polymorphisms with vitiligo.

Salivary human beta-defensins affected by oral Candida status in Chinese HIV/AIDS patients undergoing ART.

To observe relationships between oral Candida status and salivary human beta-defensin 2 and 3 (hBD-2 and hBD-3) levels in HIV/AIDS patients of Guangxi, China during the first year of antiretroviral therapy (ART) dynamically, and to understand the influence of ART on oral Candida status and salivary hBDs expressions. A prospective self-controlled study was carried to observe the dynamic changes of CD4+ T cell counts, oral Candida carriages and salivary hBD-2,3 expressions in HIV/AIDS patients during the first year of ART. A total of 90 HIV/AIDS patients were enrolled and were examined at the baseline, 3rd, 6th, 12th month of ART. Thirty healthy individuals were enrolled as control. Peripheral blood, oral rinse sample, and unstimulated whole saliva were collected to test CD4+ T cell counts, oral Candida carriages, and hBD-2,3 expressions. In the first year of ART, CD4+ T cell counts increased significantly. However, oral Candida carriages and oral candidiasis decreased significantly, and salivary hBD-2 expressions in HIV/AIDS patients decreased gradually, salivary hBD-3 levels were highly variable. Salivary hBD-2 concentrations were positively related to oral Candida carriages. The incidence of oral candidiasis among HIV/AIDS patients gradually decreased due to the immune reconstruction of ART. Salivary defensins might play an important role in Candida-host interaction in HIV/AIDS patients.

Gingival crevicular fluid levels of human beta-defensin-1 in type 2 diabetes mellitus and periodontitis.

Human β-defensin (hBD)-1 is an important gatekeeper of the gingiva against constant bacterial challenge, and glucose levels are involved in its optimal expression. The aims of the study were to investigate hBD-1 levels in gingival crevicular fluid (GCF) and to compare these levels between type 2 diabetics with or without periodontitis and healthy individuals. Altogether, 81 subjects were included in the study: 21 subjects with type 2 diabetes mellitus (T2DM) suffering from generalized periodontitis (T2DM + GP), 18 systemically healthy generalized periodontitis patients (GP), 18 periodontally healthy T2DM subjects (T2DM + H), and 24 systemically and periodontally healthy subjects (control). Plaque index (PI), gingival index (GI), probing pocket depth (PPD), and clinical attachment level (CAL) were recorded, and GCF samples were collected. hBD-1 levels in GCF were measured using ELISA. hBD-1 levels were significantly reduced in the T2DM + GP and GP groups. Although PI and GI scores were similar in both periodontally healthy groups, hBD-1 levels were lower in the T2DM + H group. In the whole population, hBD-1 levels correlated negatively with all periodontal parameters. Both diabetes and periodontitis affect hBD-1 levels in GCF. The altered levels of hBD-1 in GCF of diabetics might be associated with the susceptibility of diabetics to periodontitis.

Gingival crevicular fluid levels of human beta‐defensin 1 in individuals with and without chronic periodontitis

Human beta-defensins (hBDs) contribute to innate immunity antimicrobial activity. They are also effective in the adaptive immune response and may play a crucial role in the susceptibility to diseases of the oral cavity. This study aimed to evaluate the levels of hBD-1 in the gingival crevicular fluid of individuals with and without chronic periodontitis. Twenty periodontally healthy individuals (H) and 20 individuals with chronic periodontitis were recruited. Gingival crevicular fluid samples were collected from: healthy sites (Hh) from periodontally healthy individuals; and healthy sites (Ph), sites with gingivitis (Pg), and sites with periodontitis (Pp) from individuals with periodontitis. The levels of hBD-1 (pg/mL) were measured using enzyme-linked immunosorbent assay. Comparisons of hBD-1 between individuals (H and chronic periodontitis) and among sites (Hh, Ph, Pg, Pp) were performed through hierarchical linear modeling. Gingival crevicular fluid levels of hBD-1 were: Hh=229.52±138.96 (median 199.26), Ph=53.88±58.17 (median 35.75), Pg=57.11±40.18 (median 39.90) and Pp=55.31±37.28 (median 54.19). No influence of site diagnosis (level 1; health/gingivitis/periodontitis) was observed; however, individual diagnosis (level 2; health/periodontitis) influenced the levels of hBD-1 (P<.001). Periodontally healthy individuals showed higher gingival crevicular fluid levels of hBD-1 when compared to individuals with chronic periodontitis. This suggests a potential protective role of hBD-1 in the susceptibility to chronic periodontitis.

Comparison of Efficacy of Doxycycline and Isotretinoin on Cutaneous Human Beta-Defensin-1 and -2 Levels in Acne Vulgaris.

Background:Recent studies have shown that human beta-defensin-1 (hBD-1) and (human beta-defensin-2 hBD-2), which are antimicrobial peptides produced by the skin, play a role in the pathogenesis of acne vulgaris (AV).Objective:The aim of this study was to determine the role of antimicrobial peptides in the pathogenesis of AV and enlighten the effects of doxycycline and isotretinoin in the expression of these defensins in AV.Materials and Methods:A total of 44 patients (22 patients in each group) with Grade 6 and 8 AV who were indicated doxycycline or isotretinoin for their treatment, and 20 healthy volunteers were included in this study. Pretreatment cutaneous samples were obtained from pustular lesions and uninvolved skin of AV patients and were repeated after the treatment. Only one biopsy was obtained from controls.Results:Cutaneous levels of hBD-1 and hBD-2 were significantly increased in AV patients when compared with healthy controls (P<0.05). Doxycycline therapy achieved a decrease in hBD-1 levels (P<0.05), whereas isotretinoin therapy achieved a reduction in hBD-2 levels when compared with pretreatment levels (P<0.05). Posttreatment hBD-1 and hBD-2 levels were not different between doxycycline and isotretinoin groups (P>0.05).Conclusion:In the light of these results, it was reasonable to assume the role of hBD-1 and hBD-2 in the pathogenesis of AV. Our results showing a significant reduction in hBD-1 staining with doxycycline treatment and in hBD-2 with isotretinoin suggested that some part of their anti-acne effect worked through these mechanisms.

Effect of 0.8% Hyaluronic Acid in Conventional Treatment of Moderate to Severe Chronic Periodontitis

The aim of this study is to evaluate the effect of the subgingival application of 0.8% hyaluronic acid (HA) gel (GENGIGEL®) as an adjunct to scaling and root planing (SRP) on clinical parameters and expression of human beta defensin-2 (hBD-2) in patients with moderate to severe chronic periodontitis. In this randomized, split mouth design study, 24 participants with moderate to severe chronic periodontitis were evaluated after full mouth SRP. In the test sites 1 mL of 0.8% hyaluronan gel was applied subgingivally after SRP at baseline and 1 week post therapy. Plaque index (PI), gingival index (GI), papillary bleeding index (PBI), periodontal probing depth (PPD), and clinical attachment loss (CAL) were recorded and gingival crevicular fluid (GCF) samples were collected at baseline, after 6 and 12 weeks. Expression of human beta defensin-2 (hBD-2) was analyzed by enzyme-linked immunosorbent assay. At baseline, there were no statistical differences between test and control sites in all clinical parameters and hBD-2 expression. An improvement of PI, GI, PBI, PPD, and CAL was observed at 6 and 12 weeks (p < 0.05) in both groups. Clinically, it was noticed that all indices except CAL had more statistically significant reduction in test sites than control sites at 6 and 12 weeks. The hBD-2 levels were significantly higher in the test sites than in the control sites at 6 and 12 weeks. The local application of 0.8% hyaluronan gel with SRP have a positive effect on periodontal health of moderate to severe chronic periodontitis patients after 6 and 12 weeks. Subgingival application of 0.8% HA gel following SRP has shown anti-inflammatory effect and has a beneficial effect on clinical parameters in moderate to severe chronic periodontitis patients.

The Anti-inflammatory Effects of Glycerol-supplemented Probiotic Lactobacillus reuteri on Infected Epithelial cells In vitro.

Background:One of the most interesting effects of probiotics is their ability to modulate the immune system through the induction of cytokines and to enhance the host immune response.Aims:The purpose of this study was to evaluate the anti-inflammatory effect of glycerol-supplemented Lactobacillus reuteri on the transcription level of interleukin (IL)-8 and human-beta-defensin (hBD)-2 expressed by epithelial cells after exposure to bacteria.Materials and Methods:The confluent-cultured HaCat cell line (105 cells/mL) was exposed to Streptococcus mutans ATCC-25175 and Porphyromonas gingivalis ATCC-33277 (107 colony-forming units [CFU]/mL) for 24 h and challenged with probiotic L. reuteri ATCC-55730 (107 CFU/mL) supplemented with glycerol. Subsequently, the transcription levels of IL-8 and hBD-2 in HaCat cells were analyzed using reverse-transcription polymerase chain reaction (RT-PCR). In addition, cell viability was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. All the obtained data were statistically analyzed using the one-way analysis of variance test, with P < 0.05 set as the level of significance.Results:The MTT assays confirmed no cytotoxic effects of glycerol-supplemented L. reuteri on HaCat cells (viability >90%). mRNA expression of IL-8 and hBD-2 increased after exposure to both bacteria. The presence of glycerol-supplemented L. reuteri significantly reduced the expression of IL-8 and hBD-2 on HaCat cells (P < 0.05).Conclusion:Glycerol-supplemented L. reuteri reduced the expression of IL-8 and hBD-2, and the results may be proof of principle for a probiotic approach to combating inflammation. However, further studies are needed to validate this probiotic effect.

Comparison of IL-1β, TNF-α, hBD-2, and hBD-3 Expression in the Dental Pulp of Smokers Versus Nonsmokers

IntroductionTo date, the endodontic literature lacks research on the effect of smoking on cytokine and defensin expression in the dental pulp. Therefore, the aim of this study was to investigate the expression of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, human beta defensin (hBD)-2 and hBD-3 in the dental pulp of smokers and compare them with nonsmokers. We hypothesized that cytokine and defensin expression would be reduced in smokers as compared with nonsmokers. MethodsThirty-two smokers and 37 nonsmokers with endodontic pulpal diagnoses of normal, symptomatic irreversible pulpitis and asymptomatic irreversible pulpitis were included in this cross-sectional study. Samples from pulp chambers were collected and stored in phosphate-buffered saline at −80°C. Luminex was used to measure IL-1β and TNF-α levels. The levels of hBD-2 and hBD-3 were measured using enzyme-linked immunosorbent assay. Marker levels were normalized to protein concentrations and data were analyzed using Kruskal-Wallis test, Mann-Whitney U test, and 2-way analysis of variance (α = 0.05). ResultsPulpal concentrations of TNF-α and hBD-2 were significantly lower among smokers (P < .01), whereas no significant difference was observed for IL-1β, or hBD-3. Two-way analysis of covariance revealed that smoking status (P < .001), not endodontic diagnosis (pulpal status), significantly affected TNF-α and hBD-2 levels. ConclusionsThis study reported that smokers are immunologically deficient in TNF-α and hBD-2, suggesting that dental pulps of smokers possess limited defense mechanisms, affecting their endodontic prognosis and indicating a cause for their reported inferior outcome.

Cervicovaginal Levels of Human β-Defensin 1, 2, 3, and 4 of Reproductive-Aged Women With Chlamydia trachomatis Infection.

This study included women attending primary health care units in Botucatu, São Paulo, Brazil, to assess the cervicovaginal levels of human β-defensin (hBD) 1, 2, 3, and 4 during Chlamydia trachomatis infection. Cervicovaginal samples were collected for Pap testing and assessing the presence of infection by C. trachomatis, human papillomavirus, Neisseria gonorrhoeae, and Trichomonas vaginalis. Vaginal smears were taken to evaluate local microbiota. Human β-defensin levels were determined using enzyme-linked immunosorbent assay in cervicovaginal fluid samples. Seventy-four women with normal vaginal microbiota and no evidence of infection were included in hBD quantification assays; 37 tested positive for C. trachomatis and 37 were negative. Statistical analysis was performed using Mann-Whitney U test. Women positive for C. trachomatis had significantly lower cervicovaginal hBD-1, hBD-2, and hBD-3 compared with those who tested negative (hBD-1: 0 pg/mL [0-2.1] vs 1.6 pg/mL [0-2.4], p < .0001; hBD-2: 0 pg/mL [0-3.9] vs 0.61 pg/mL [0-8.9], p = .0097; and hBD-3: 0 pg/mL [0-4.3] vs 0.28 pg/mL [0-8.4], p = .0076). Human β-defensin 4 was not detected. Lower levels of hBD-1, hBD-2, and hBD-3 in cervicovaginal fluid were detected in the presence of C. trachomatis infection.

Serum Human Beta-Defensin-2 Is a Possible Biomarker for Monitoring Response to JAK Inhibitor in Psoriasis Patients

Aims: To analyse the correlation between serum human beta-defensin-2 (hBD-2) levels and response to JAK inhibitor in psoriasis. Methods: We evaluated the psoriasis area and severity index (PASI) and serum hBD-2 levels of 18 psoriasis patients randomized to receive placebo or tofacitinib 5 or 10 mg b.i.d. at baseline, week 8, and week 16. Serum hBD-2 levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: The PASI achieved a dramatic reduction after tofacitinib 5 or 10 mg b.i.d. treatment for 16 weeks (p < 0.05). Serum hBD-2 levels significantly decreased in patients treated with tofacitinib 10 mg b.i.d. compared with baseline and the placebo-treated patients (p < 0.05). A significant correlation was found between hBD-2 levels and PASI (r = 0.52, p < 0.01). A serum hBD-2 level of 1,255.45 pg/mL was a cut-off between mild and moderate-to-severe psoriasis in ROC analysis. Conclusions: Serum hBD-2 level might be a possible biomarker for monitoring psoriasis treatment response and differentiating mild from moderate-to-severe psoriasis.

Atopic Dermatitis-like Graft-versus-host Disease and Lichen Planus-like Graft-versus-host Disease: Alterations in Skin Barrier Function and Related Molecules.

Background:Graft-versus-host disease (GVHD) is a common complication of hematopoietic stem cell transplantation. Skin barrier disruption could induce thymic stromal lymphopoietin (TSLP) expression, and the expression of TSLP was increased in lesions of atopic dermatitis (AD)-like GVHD and lichen planus (LP)-like GVHD. This study attempted to investigate the skin barrier function of AD-like GVHD and LP-like GVHD and possible mechanisms.Methods:Eighteen AD-like GVHD patients, 12 LP-like GVHD patients, and 14 healthy volunteers were enrolled in this study. Skin biopsy was done in five AD-like GVHD patients, eight LP-like GVHD patients, and eight healthy volunteers. The intensity of pruritus was assessed by visual analog scale itch score and detailed pruritus score. Transepidermal water loss (TEWL) was measured using Tewameter® TM 300. Immunohistochemistry was used to observe the expression of loricrin, involucrin, LL37, and human β-defensins 2 (hBD2) in skin lesions. Western blot analysis was used for analyzing the protein levels of loricrin and involucrin in skin lesions. Real-time polymerase chain reaction was performed to assess the mRNA levels of LL37 and hBD2 in skin lesions.Results:Pruritus score was higher in patients with AD-like GVHD (11.33 ± 5.35) than that of patients with LP-like GVHD (2.58 ± 3.09, P < 0.001). Compared with healthy controls (HCs, 4.52 ± 1.24 g·m−2·h−1), TEWL was increased in AD-like GVHD (26.72 ± 9.02 g·m−2·h−1, P < 0.001) and LP-like GVHD patients (18.78 ± 4.57 g·m−2·h−1, P < 0.001), and expressions of loricrin and involucrin were also increased in skin lesions of AD-like GVHD and LP-like GVHD patients (all P < 0.05). LL37 mRNA expression was decreased in lesions of AD-like GVHD and LP-like GVHD patients (P = 0.005 and P = 0.008, vs. HCs, respectively). hBD2 mRNA expression was increased in skin lesions of AD-like GVHD and LP-like GVHD patients (P = 0.002 and P < 0.001, vs. HCs, respectively).Conclusions:Skin barrier dysfunction is present in AD-like GVHD and LP-like GVHD. The immunoreactions, but not the congenital defect, are considered to be the primary cause of skin barrier impairment in AD-like GVHD and LP-like GVHD.

Human β-defensin-3 induces IL-8 release and apoptosis in airway smooth muscle cells.

Human airway smooth muscle cells (ASMCs) may have a pro-inflammatory role through the release of inflammatory mediators. Increasing evidence indicates that human β-defensins (HBDs) are related to pathogenesis of asthma. To examine the plasma level of HBD-1, HBD-2 and HBD-3 in asthmatic patients and the expression of their mouse orthologues in the lung tissue of a mouse model of chronic severe asthma. Further to investigate the effect of HBD-3 on the release of the pro-inflammatory cytokine IL-8 and to explore the mechanisms. The plasma levels of HBD-1, HBD-2 and HBD-3 from 34 healthy controls and 25 asthmatic patients were determined by ELISA. The expression of mouse β-defensins MBD-1, MBD-3 and MBD-14 in the lung tissue of asthmatic mice was detected by Western blot. The ASMCs were cultured with HBD-3 for 24hour, and then the supernatant level of IL-8 was evaluated by ELISA and the cell viability was examined by WST-1 assay. The signalling pathway was investigated with blocking antibodies or pharmacological inhibitors. The plasma levels of HBD-1 and HBD-3 were elevated in asthmatic patients, and the expression of MBD-14, the mouse orthologue for HBD-3, was increased in asthmatic mice. HBD-3-induced IL-8 production in a CCR6 receptor-specific manner and was dependent on multiple signalling pathways. Moreover, HBD-3-induced cell apoptosis concurrently, which was dependent on the ERK1/2 MAPK pathway. Mitochondrial ROS regulated both HBD-3-induced IL-8 production and cell apoptosis. These observations provide clear evidence of an important new mechanism for the promotion of airway inflammation and tissue remodelling with potential relevance for the treatment of asthma.

Human β-Defensin 2 in Primary Sclerosing Cholangitis.

Objectives:Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the bile ducts frequently associated with inflammatory bowel disease (IBD), suggesting an important role for the gut–liver axis. Defensins are small (3.5–4.5 kDa) anti-microbial peptides that contribute to innate immunity at mucosal surfaces and have been implicated in IBD. The aim of this study was to investigate copy number variation of the gene (DEFB4) encoding human β-defensin 2 (HBD2) and protein expression of HBD2 in PSC.Methods:US and Italian PSC cases and unaffected controls (US PSC patients n=89, US controls n=87; Italian PSC patients n=46, Italian controls n=84) were used to estimate HBD2 gene copy number by both quantitative real-time PCR and paralog ratio test. Serum levels of HBD2 were measured by enzyme-linked immunosorbent assay and liver expression was analyzed by immunohistochemistry.Results:Mean serum levels of HBD2 were significantly greater in PSC (1,086±1,721 ng/μl) compared with primary biliary cholangitis (544±754 ng/μl), ulcerative colitis (417±506 ng/μl), and healthy controls (514±731 ng/μl) (P=0.02). However, no significant differences between the frequencies of high DEFB4 gene copy number, defined by >4 copies, and PSC were found in the US, Italian, or combined cohorts. Importantly, a high number of biliary ducts were found immunopositive in PSC samples compared with controls.Conclusions:Our data show that HBD2 serum levels and tissue expression are increased in PSC subjects, suggesting that this arm of innate immunity may be important in the etiopathogenesis of PSC.

Associations between HBD3 and Pro-Inflammatory Cytokines in Asymptomatic Irreversible Pulpitis

Objective: The aim of this study was to investigate the levels of Human Beta Defensin (hBD) 2 and 3, chemokine and cytokine expressions between teeth endodontically diagnosed with symptomatic irreversible pulpitis (SIP), asymptomatic irreversible pulpitis (ASIP) and normal pulps. We hypothesized that there would be a correlation between hBD’s and the immunoregulatory response. Design: Pulpal samples were collected with paper points. Six samples were obtained from normal teeth, 21 from SIP, 18 from ASIP. Levels of cytokines and betadefensins were measured by Luminex technology and ELISA, respectively. Data were statistically analyzed using Kruskal-Wallis, Wilcoxon Mann-Whitney test and Spearman correlation test. Differences were considered significant at p&lt;0.05. Results: hBD-2 levels correlated with samples obtained from patients in the ASIP group, but not in the samples obtained from patients with SIP or the control group. HBD-3 concentrations associated with all of the cytokines and chemokines in both SIP and ASIP groups. However, in the normal group, hBD-3 correlated with only TNFα, IL-8, MCP-1, IL-1β, MIP-1a, RANTES, IL-17 in normal group. When comparing control levels of hBD-2 and hBD-3 with patients samples from either the ASIP or the SIP groups, hBD-2 and hBD-3 concentrations were highest in the ASIP group. Conclusions: The hBD-2 and-3 were highly associated with the levels of the chemokines and cytokines in ASIP group. HBD-3 concentrations correlate with the levels of the chemokines and the cytokines in the SIP and ASIP groups.

The investigation of antimicrobial peptides expression and its related interaction with methotrexate treatment in patients with psoriasis vulgaris

Background: Psoriasis is a chronic, inflammatory and immune-mediated disease. Recently, the role of antimicrobial peptides (AMPs) such as human beta defensins (hBDs) in the pathogenesis of psoriasis has been investigated. We aimed to evaluate the expression profiles of hBD-1 and hBD-2 in psoriatic skin before and after methotrexate (MTX) therapy and to compare healthy controls.Methods: Immunohistochemical expressions of hBD-1 and hBD-2 were assessed in 16 patients with psoriasis vulgaris and 20 normal skin biopsies from healthy controls. The patients were administered a 12 week of MTX and skin biopsy samples were obtained from the lesional skin of the patients pre-/posttreatment and normal body of the healthy controls.Results: The median (range) Psoriasis Area and Severity Index (PASI) value was 21.6 (8.2–27.7) before the treatment whereas; 3.05 (1–23.4) after the treatment. hBD-1 expression in psoriasis patients was significantly higher as compared to the healthy controls before treatment (p < 0.01). No significant difference was observed between psoriasis patients and healthy controls in terms of hBD-2 expression before treatment (p > 0.05). No significant difference was observed between before–after MTX treatment in terms of hBD-1 and hBD-2 expression levels in psoriasis patients (p > 0.05).Conclusions: These findings suggest a role for hBD-1 in psoriasis pathogenesis. But MTX treatment does not affect on hBD-1 and hBD-2 expressions. Further studies are needed to assess the roles of these AMPs in psoriasis etiopathogenesis.

VAGINAL BIOCENOSIS IN PREGNANT WOMEN

Bacterial vaginosis developing in pregnancy is associated with abnormal vaginal flora and with an imbalance of cytokines and antimicrobial peptides. The aim of this research was to study the bacterial, cytokine and antimicrobial components of the vaginal nonspecific immune system in the second and third trimesters of pregnancy among patients with recurrent bacterial vaginosis. Materials and methods . The study included 40 pregnant women with recurrent bacterial vaginosis (Group 1), and 40 healthy pregnant women with no signs of vaginosis (Group 2). At the onset of this study, the average gestational age among the selected women was 14.8 ± 2.0 weeks. We analyzed clinical and laboratory parameters of bacterial vaginosis, qualitative and quantitative characteristics of the vaginal flora, the levels of β-defensin-2 (HBD-2), interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), and interferon-γ (INF-γ) in vaginal washouts. Results. The pregnant women with recurrent bacterial vaginosis tested at the 30th week of gestation, had moderate vaginal dysbiosis caused by an increased number of anaerobic microorganisms. Along with that, at the beginning of the third trimester, the number of lactobacillus bacteria increased in both Group 1 and Group 2. Notably, the predominant species in the healthy women samples was L. crispatus whereas in patients with recurrent bacterial vaginosis that was L. iners. There were no changes in the levels of cytokines and antimicrobial peptide between the second and third trimester in women with recurrent bacterial vaginosis. In this group (Group 1), however, the levels of HBD-2, IL-1β, IL-6, IL-10, INF-γ were lower in comparison with healthy pregnant women (Group 2), which can be seen as a risk factor of further returns of the disease. Conclusion. Pregnant women with recurrent bacterial vaginosis as well as women with normal course of gestation have an increased presence of lactobacilli bacteria in their vagina during the third trimester of gestation. No other changes in the bacterial, antimicrobial and cytokine components of the nonspecific immune system in the female reproductive tract were found.

Serum inflammatory biomarkers fail to identify early axial spondyloarthritis: results from the SpondyloArthritis Caught Early (SPACE) cohort

IntroductionDecreasing the diagnostic delay in axial spondyloarthritis (axSpA) remains a major challenge. Here, we assessed the value of serum inflammatory biomarkers to distinguish early axSpA from other pathologies in a...

Implication of vitamin D-associated factors in patients with non-tuberculous mycobacterial lung disease.

Little information is available regarding vitamin D-associated factors in patients with non-tuberculous mycobacteria (NTM) lung disease. To determine the association between vitamin D-related factors and susceptibility to NTM lung disease. The relative gene expression levels of cathelicidin (CAMP), defensin (DEFB4), vitamin D receptor (VDR) and 1-hydroxylase (CYP27B1), as well as the serum levels of 25-hydroxyvitamin D (25[OH]D), cathelicidin (LL-37), defensin (hBD-2) and vitamin D-binding protein (DBP) from 82 patients with NTM lung disease and 28 control subjects were analysed. Gene expression of CAMP and DEFB4 was significantly higher, and gene expression of VDR and CYP27B1 was significantly lower, in NTM patients than controls. Serum LL-37 and hBD-2 levels were not significantly different between NTM patients and controls; however, the serum DBP level was higher in NTM patients than controls. The serum vitamin D status of patients did not correlate with serum LL-37, hBD-2, or DBP concentration or gene expression of CAMP, DEFB4, VDR or CYP27B1. A higher level of gene expression for antimicrobial peptide is more likely to be associated with NTM lung disease than serum vitamin D status.

Adiponectin corrects premature cellular senescence and normalizes antimicrobial peptide levels in senescent keratinocytes

Stress-induced premature senescence or aging causes dysfunction in the human somatic system. Adiponectin (Acrp30) plays a role in functional recovery, especially with adenosine 3′,5′-monophosphate (AMP)-activated protein kinase (AMPK) and silent mating type information regulation 2 homolog 1 (SIRT1). Acrp30 stimulation reduced the premature senescence positive ratio induced by hydrogen peroxide (H2O2) and restituted human β-defensin 2 (hBD-2) levels in senescent keratinocytes. Acrp30 recovered AMPK activity in senescent keratinocytes and increased SIRT1 deacetylation activity. As a result, FoxO1 and FoxO3 transcription activity was recovered. Additionally, Acrp30 stimulation suppresses NFκB p65, which induces abnormal expression of hBD-2 induced by H2O2. In the present study, we have shown that Acrp30 reduces premature senescence and recovers cellular function in keratinocytes. These results suggest a role for Acrp30 as an anti-aging agent to improve impaired skin immune barriers.

Flagellin Induces β-Defensin 2 in Human Colonic Ex vivo Infection with Enterohemorrhagic Escherichia coli.

Enterohemorrhagic E.coli (EHEC) is an important foodborne pathogen in the developed world and can cause life-threatening disease particularly in children. EHEC persists in the human gut by adhering intimately to colonic epithelium and forming characteristic attaching/effacing lesions. In this study, we investigated the innate immune response to EHEC infection with particular focus on antimicrobial peptide and protein expression by colonic epithelium. Using a novel human colonic biopsy model and polarized T84 colon carcinoma cells, we found that EHEC infection induced expression of human β-defensin 2 (hBD2), whereas hBD1, hBD3, LL-37, and lysozyme remained unchanged. Infection with specific EHEC deletion mutants demonstrated that this was dependent on flagellin, and apical exposure to purified flagellin was sufficient to stimulate hBD2 and also interleukin (IL)-8 expression ex vivo and in vitro. Flagellin-mediated hBD2 induction was significantly reduced by inhibitors of NF-κB, MAP kinase p38 and JNK but not ERK1/2. Interestingly, IL-8 secretion by polarized T84 cells was vectorial depending on the side of stimulation, and apical exposure to EHEC or flagellin resulted in apical IL-8 release. Our results demonstrate that EHEC only induces a modest immune response in human colonic epithelium characterized by flagellin-dependent induction of hBD2 and low levels of IL-8.