Interleukin 14 Research Articles

Clinical diagnostic value of IL-14, 1L-16 and SAA in periodontitis.

Periodontitis is a chronic infectious disease, which leads to inflammatory destruction of periodontal supporting tissues. Interleukin 14 (IL-14), Interleukin 16 (IL-16) and serum amyloid A (SAA) have been demonstrated to be abnormally expressed in inflammatory diseases. Therefore, this study was performed to analyzed the expression and potential clinical values of IL-14, 1L-16 and SAA in periodontitis. A total of 100 periodontitis patients and 100 healthy volunteers were recruited and the saliva and serum samples were collected. Then the C-reactive protein (CRP), procalcitonin (PCT), IL-14, 1L-16 and SAA levels in the saliva and serum of periodontitis patients were measured by Elisa kits. Besides, the significance of CRP, PCT, IL-14, 1L-16 and SAA in periodontitis patients were analyzed by receiver operating characteristic (ROC) analysis. The results showed that CRP, PCT, IL-14, 1L-16 and SAA levels were significantly increased in the the saliva and serum of the periodontitis patients. Additionally, the area under the curve (AUC) of saliva CRP, PCT, IL-14, 1L-16 and SAA for the diagnosis of periodontitis were 0.9035, 0.9435, 0.9508, 0.9500 and 0.9467, respectively. The AUC of serum CRP, PCT, IL-14, 1L-16 and SAA for the diagnosis of periodontitis were 0.9035, 0.9435, 0.9508, 0.9500 and 0.9467, respectively. What's more, the diagnostic value of IL-14, 1L-16 and SAA were enhanced when combining with CRP and PCT. This study demonstrated that IL-14, IL-16 and SAA expressions were upregulated in periodontitis patients and exhibited a significant significance for periodontitis diagnosis.

Oxytocin and Interleukin-14: New suggested indicators for prediction of type 2 diabetes-induced nephropathy

Diabetes is one of the major risk factors for chronic renal failure (CRF). The present work involved studying the effect of lifestyle factors such as (age, gender, smoking and area of residence) which can affect chronic renal diseases. Also, the study estimated Oxytocin (Oxt) and Interleukin-14 (IL-14) using the sandwich ELISA technique in the serum of type 2 diabetic patients with CRF who presented to hemodialysis and a control group. Blood samples of (50) diagnosed type 2 diabetic patients with CRF from both sexes were compared with (40) samples from healthy individuals as a control group. The results demonstrated significant elevation (p<0.05) in Oxt and IL-14 concentrations for patients with CRF compared to the control group. As for the subgroups, the statistical test showed a significant difference (p < 0.05) when comparing Oxt levels between the same sex in the two groups. While no significant difference was observed when comparing IL-14 in the same or the two groups. The parameters Oxt and IL-14 are necessary tools for predicting renal failure. Keywords: Oxytocin, Interleukin-14, Type 2 Diabetes Mellitus, Hemodialysis

Conditionally induced RAGE expression by proximal airway epithelial cells in transgenic mice causes lung inflammation.

BackgroundReceptors for advanced glycation end-products (RAGE) are multiligand cell-surface receptors expressed abundantly by distal pulmonary epithelium. Our lab has discovered RAGE-mediated effects in the orchestration of lung inflammation induced by tobacco smoke and environmental pollutants; however, the specific contribution of RAGE to the progression of proximal airway inflammation is still inadequately characterized.Methods and resultsWe generated a Tet-inducible transgenic mouse that conditionally overexpressed RAGE using the club cell (Clara) secretory protein (CCSP) promoter expressed by club (Clara) cells localized to the proximal airway. RAGE was induced for 40 days from weaning (20 days of age) until sacrifice date at 60 days. Immunohistochemistry, immunoblotting, and qPCR revealed significant RAGE up-regulation when compared to non-transgenic controls; however, H&E staining revealed no detectible morphological abnormalities and apoptosis was not enhanced during the 40 days of augmentation. Freshly procured bronchoalveolar lavage fluid (BALF) from CCSP-RAGE TG mice had significantly more total leukocytes and PMNs compared to age-matched control littermates. Furthermore, CCSP-RAGE TG mice expressed significantly more tumor necrosis factor alpha (TNF-α), interleukin 7 (IL-7), and interleukin 14 (IL-14) in whole lung homogenates compared to controls.ConclusionsThese data support the concept that RAGE up-regulation specifically in lung airways may function in the progression of proximal airway inflammation.

Regulation of Human Interleukin 14 Transcription In Vitro and In Vivo After Renal Transplantation

Alloantibodies and B lymphocytes are felt to contribute in increasingly important ways to the pathogenesis of both acute and chronic allograft injury. The mechanisms that lead to the formation of posttransplant alloantibodies despite immunosuppressive therapy have not been fully elucidated. Interleukin 14 (IL-14) or high molecular weight B cell growth factor secreted by activated T and B cells and follicular dendritic cells promotes B cell growth, survival and memory, and antibody production. The potential role of IL-14 in human transplantation has not been examined. Using quantitative polymerase chain reaction techniques, we examined IL-14 mRNA transcript levels in human cells and compared them to IL-2. Interleukin-14 mRNA levels were measured in isolated human T cells stimulated in vitro with mitogen and alloantigen in the presence or absence of immunosuppressive drugs. In vivo, IL-14 transcript levels were measured in peripheral blood leukocytes isolated from patients after renal transplantation. In vitro, both IL-14 and IL-2 transcript levels increase after alloantigen and mitogen stimulation and are suppressed by currently used immunosuppressive agents. In vivo, IL-14 and IL-2 behave differently as IL-14 transcript levels are not reduced by immunosuppressive therapy. Interleukin-14 transcripts also increase after both immune and nonimmune injury to renal allografts. This is the first demonstration of human IL-14 mRNA regulation in vitro and in vivo. Given the important effects of IL-14 on B cell proliferation and antibody production, increases in IL-14 transcript levels may play a role in alloantibody formation after renal transplantation.

IL-14 RNA Levels in the Peripheral Blood Leukocytes of Patients with SLE

RATIONALE: Interleukin 14 (IL-14) is a cytokine produced predominantly by activated T lymphocytes and follicular dendritic cells which enhances the proliferation of germinal center B-lymphocytes and the survival of “memory” B-lymphocytes in vitro. Transgenic mice expressing IL-14 with pEμSV (predominantly in B cells) develop features of SLE and Sjögren syndrome. In this study, we evaluated IL-14α and IL-14β expression in the peripheral blood leukocytes of patients with SLE. METHODS: Total RNA was isolated from the peripheral blood leukocytes of 22 SLE patients and 5 normal controls. Quantitative PCR was utilized to quantify the RNA for IL-14α and IL-14β. RESULTS: Across the entire patient population, IL-14α and IL-14β RNA levels were no different than that of normal controls. However, IL-14 β RNA levels were higher in patients with predominantly skin disease (P=0.03) and in those with inactive disease (P=0.02). Patients with kidney involvement had lower IL-14α RNA levels (P=0.04). There were direct correlations between IL-14α and IL-14β RNA levels and the absolute lymphocyte counts. CONCLUSIONS: Differences in levels of IL-14α and IL-14β RNA levels in leukocyte of SLE patients and normal controls correlated predominantly with the lymphocyte count. Additional studies should be done using purified lymphocyte to determine whether the expression of these genes in lymphocytes correlates with particular disease manifestations or activity of SLE.

Development of a Blastoid Variant, Mantle Cell Lymphoma Model in Transgenic Mice.

Mantle Cell Lymphoma (MCL) is a poorly understood, aggressive histotype of B-cell non-Hodgkin's Lymphomas (NHL-B) that remains the most therapeutically resistant of the NHL-B. Little is known regarding why MCL is so clinically aggressive and therapeutically refractory. Blastoid variant MCL (MCL-BV) is an even more aggressive form of MCL that appears to be increasing in incidence in the US. It may represent progression from classic MCL, often with leukemic involvement and complex lymphoma karyotypes. Interleukin 14 (IL-14) is cytokine that was identified and cloned from a Burkitt lymphoma (BL) cell line that acts as a growth factor for normal B-lymphocytes. The expression of IL-14a protein and mRNA levels are elevated at lease fifty-fold in B-cell non-Hodgkin's Lymphomas (NHL-B), including mantle cell lymphoma (MCL), in contrast to very low levels of IL-14a in quiescent (Go) B cells by both western and northern blot analysis. To evaluate the role of IL-14 in vivo, we have generated transgenic mice expressing IL-14 with pEuSR. The IL-14 TG mice generally live a normal life span, however when autopsies are performed at 18 months of age, splenomegaly is noted, and 50% have evidence of B cell lymphoma. This lymphoma is CD5+, CD19+, sIgM+, CD21− and contains a monoclonal population of B-lymphocytes with rearranged immunoglobulin genes. Morphologically the lymphoma arising in IL-14 transgenic mice resembles the centroblastic/Immunoblastic histotype of DLBCL. Because of the frequent involvement of c-myc in various B cell malignancies, we crossed Eμ-myc (c-myc TG) mice with the IL-14 TG mice. By 3 months of age, 100% of the double transgenic (DTG) mice develop an aggressive B cell malignancy that is characterized by extensive lymphadenopathy and splenomegaly with intermediate to large atypical lymphoid cells, strongly resembling MCL-BV morphologically. This tumor, like that derived from the IL-14 TG mice, is CD5+, CD19+, sIgM+, CD21−. It is also CD23− and over-expresses Cyclin D1 in monoclonal B lymphoid cells with re-arranged IgH immunoglobulin genes, mimicking the MCL phenotype. At the time of autopsy, tumor infiltration of DTG mice is generally found in all organs evaluated, including peripheral blood, lymph nodes, spleen, liver, bone marrow, thymus and kidneys, consistent with the usual findings in MCL-BV. No tumors are observed in IL-14α TG or c-myc TG mice autopsied at this age. This MCL-BV model allows for the molecular and genotypic characterization of the murine B lymphoid cell compartment from birth to lymphoma development (3 mos.), including histogenesis and functional determination of the growth and survival characteristics of these tumors in DTG bone marrow and peripheral B cell populations. Preliminary comparative in vitro and in vivo (SCID Xeno-transplants) studies in DTG/MCL-BV lymphomas have shown additional molecular similarities to the pathophysiology (e.g constitutive NF-kB activation) of MCL-BV cell lines and patient samples, that should provide insights for future potential therapeutic approaches to MCL.

Constitutive expression of interleukin 14 (IL-14) in transgenic mice leads to enhanced responses to vaccinations and autoimmunity

RATIONALE: We have previously described human interleukin 14 (IL-14) as a B cell growth factor. In vitro studies suggested that IL-14 might be important in inducing memory B cell responses. Increased expression of IL-14 was demonstrated in patients with SLE, who have memory responses to autoantigens. Transgenic mice were developed expressing IL-14 to evaluate vaccination responses and the development of autoimmunity in vivo.

A Potential Role for PGE and IL-14 (HMW-BCGF) in B-Cell Hyperactivity of Patients with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a disease characterized by the prolonged production of high-affinity autoantibodies resulting in direct and immune complex-mediated tissue damage. Because autoantibody responses occur over several years, memory B cells are likely to be involved. Interleukin-14 (IL-14) is a cytokine implicated in the generation and maintenance of normal memory B cells. Many of the actions of IL-14, including inhibition of antibody synthesis and upregulation of IL-14 receptors (IL-14R), are dependent on the formation of prostaglandin E (PGE) and subsequently cAMP. We observed that IL-14 induces phospholipase A(2) (PLA(2))-dependent release of arachidonic acid from phosphatidylcholine and phosphatidylinositol. Production of PGE is blocked by the PLA(2) inhibitor bromophenacyl bromide. Exogenous PGE (misoprostol) induces similar inhibition of antibody synthesis and increases in IL-14R as IL-14. Lymphocytes from patients with inactive SLE were noted to spontaneously produce PGE. Lymphocytes from normal donors produced PGE only after Sac-activation and IL-14 stimulation. Peripheral B and T lymphocytes from SLE patients, but not normal donors, spontaneously produced IL-14. Increased numbers of peripheral B lymphocytes from patients with inactive SLE expressed IL-14R, when compared to normal donors. Thus, increased production of IL-14 and PGE in SLE may result in expansion of a memory B-cell population capable of long-term autoantibody production. Further study will be necessary to confirm these preliminary findings and to examine in greater depth the regulation of PGE and IL-14 in SLE patients and normal donors.

Identification of B-Cell Growth Factors (Interleukin-14; High Molecular Weight-B-Cell Growth Factors) in Effusion Fluids From Patients With Aggressive B-Cell Lymphomas

The molecular basis of neoplastic B-cell growth is complex and poorly understood. Cytokines have been postulated to contribute to neoplastic cell growth, and many in vitro studies have confirmed this prediction, but little is known about the in vivo role of these growth factors. We have examined the production of interleukin-14 (IL-14) (high molecular weight [HMW], B-cell growth factor [BCGF]) by aggressive intermediate (diffuse large cell) lymphomas of the B-cell type non-Hodgkin's lymphoma (NHL-B) in four patients with lymphomatous effusions. In these studies, IL-14 was detected in the effusion fluids by Western blots and IL-14 mRNA was constitutively expressed in the freshly isolated lymphoma cells that also expressed the receptor for IL-14 (IL14R). Lymphoma B cells placed at low serum and cell density proliferated in vitro to either purified IL-14 or IL-14 derived from effusion fluids. Antibodies to IL-14 removed the growth-stimulating cytokine(s) from the effusions. Cell lines developed from these patients produced IL-14 in vitro and antisense oligos to IL-14 blocked their growth in vitro. Thus, autocrine or paracrine production of IL-14 may play a significant role in the rapid proliferation of aggressive NHL-B. Interrupting this pathway could be a useful goal of therapy for patients resistant to conventional chemotherapy.