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Pulmonary fibrosis is a kind of pulmonary disorder with chronic inflammation and excessive collagen deposition, and its etiology is not clear. Interleukin (IL)-38 is a new member of IL-1 family cytokines, but its role in pulmonary fibrosis has not been elucidated. In this study, a lentivirus expressing IL-38 was injected into the nasal cavity of mice with bleomycin-induced pulmonary fibrosis. We found that IL-38 overexpression reduced the body weight loss and improved the survival of mice induced by bleomycin. Furthermore, IL-38 expression attenuated the pulmonary inflammation and fibrosis damage induced by bleomycin, decreased the production of pro-inflammatory and pro-fibrotic cytokines such as IL-1β, IL-6, IL-17A, monocyte chemoattractant protein-1, and tumor necrosis factor-α, but increased the release of anti-inflammatory cytokine IL-1 receptor antagonist (IL-1Ra) in the lungs of bleomycin-challenged mice. Our data suggest that IL-38 may inhibit bleomycin-induced pulmonary inflammation and fibrosis through its anti-inflammatory effect and regulation of IL-1β/IL-1Ra balance, and IL-38 may be a new strategy for the treatment of pulmonary fibrosis.

This study determined the effects of paeoniflorin (PF) on the expression of purinergic receptor P2X ligand-gated ion channel 7 (P2X7R) expressed on peripheral blood mononuclear cells (PBMCs) and production of ATP-induced pro-inflammatory cytokines released by PBMCs in patients with primary Sjögren's syndrome (pSS). The pharmacological functions and cytotoxic effects of PF were dose dependent in PBMCs from 20 newly diagnosed pSS patients and 20 normal individuals. The optimum dose of PF was 100μM. PF significantly down-regulated the production of interleukin (IL)-1β and IL-6 from pSS PBMCs, and significantly inhibited ATP-induced expression of P2X7R, that might contribute to reduced IL-1β and IL-6. mRNA and protein levels of P2X7R on pSS PBMCs were significantly higher than in normal individuals (p=0.03, p<0.001). When PBMCs from subjects were stimulated in vitro with ATP in the presence of PF, P2X7R mRNA and protein levels were decreased significantly (p<0.001, p<0.001, respectively versus ATP group) in the pSS. Supernatant IL-1β and IL-6 levels were significantly lower in the PF group compared with ATP group (p<0.001, p<0.001). We show for the first time that PF-mediated reduction of IL-1β and IL-6 was due in part to the reduced expression and activation of the ATP sensor P2X7R on pSS PBMCs, indicating that PF might be useful for the management of pSS via down-regulating P2X7R expression. Thus, PF may provide a new therapeutic approach to regulate P2X7R-mediated pathologic responses of pSS., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Interleukin- (IL-) 38 is a recently discovered cytokine and is the tenth member of the IL-1 cytokine family. IL-38 shares structural features with IL-1 receptor antagonist (IL-1Ra) and IL-36Ra. IL-36R is the specific receptor of IL-38, a partial receptor antagonist of IL-36. IL-38 inhibits the production of T-cell cytokines IL-17 and IL-22. IL-38 also inhibits the production of IL-8 induced by IL-36γ, thus inhibiting inflammatory responses. IL-38-related cytokines, including IL-1Ra and IL-36Ra, are involved in the regulation of inflammation and immune responses. The study of IL-38 and IL-38-related cytokines might provide new insights for developing anti-inflammatory treatments in the near future.

A system for the production of soluble interferon (IFN)-lambda2 was developed by fusing the IFN-lambda2, NusA protein, polyhistidine and S peptide genes and then expressing the fused product (Nus-His-S-tagged IFN-lambda2) in Escherichia coli. The expressed fusion protein was purified by Ni-NTA affinity chromatography. The fusion tag was removed from recombinant IFN-lambda2 by cleavage with enterokinase. N-Terminal sequencing confirmed the identity of the purified protein. When compared with commercial IFN-alpha2b, IFN-lambda2 had similar antiviral activity. The production and characterization of biologically active IFN-lambda2 will be beneficial for its potential role in clinical applications.

Human interleukin (IL)-29 is the latest member of the class II cytokine family. However, as a result of lacking efficient method to generate relatively large quantity of IL-29, little is known of its functions in man. In the present study, an Escherichia coli expression system for the rapid expression of the human IL-29 gene was developed. It involved of cloning IL-29 gene into the pET-44 Ek/LIC vector, which allowed expression of IL-29 with a fusion tag consisting of the NusA protein, polyhistidine and S peptide (Nus-His-S-tag), and introducing a thrombin recognition site between the fusion tag and IL-29. The expressed fusion protein was purified by S-protein agarose affinity chromatography, and the fusion tag was removed from recombinant IL-29 by cleavage with thrombin. The purified IL-29 appeared a single band on SDS-PAGE, and the yield of IL-29 was 60 mg from 1 l of bacterial culture. N-terminal sequencing confirmed the identity of the purified protein. The recombinant IL-29 showed specific antiviral activity that was comparable to the commercially available IFN alfa-2b preparation.

Aim. Interleukin (IL)-37 is a new anti-inflammatory cytokine of the IL-1 family. This study aimed to determine the effects of IL-37 on acetaminophen (APAP)-induced liver injury. Materials and Methods. IL-37 plasmids were injected into mice via a tail vein hydrodynamics-based gene delivery. Results. Our results showed that IL-37 pretreatment significantly decreased serum alanine aminotransferase and aspartate aminotransferase levels, hepatic myeloperoxidase activity, and attenuated the histological liver damage. Compared to the APAP group, IL-37 administration decreased Kupffer cells numbers in the liver of APAP-induced hepatotoxicity in mice. Furthermore, IL-37 pretreatment reduced the expression of proinflammatory cytokines including tumor necrosis factor-α, IL-6, IL-17, and nuclear factor-κB (NF-κB) in APAP-induced mice. Conclusion. These results demonstrate that delivery of IL-37 plasmid can ameliorate APAP-induced liver injury by reducing proinflammatory cytokines production and preventing the activation of the NF-κB signaling pathway. IL-37 may be a promising candidate against APAP-induced liver injury. [ABSTRACT FROM AUTHOR]

The mechanism by which cigarette smoke ( CS) causes chronic obstructive pulmonary disease ( COPD) is poorly understood. Interleukin-33 ( IL-33) is a pleiotropic cytokine predominantly expressed in lung tissue and can elicit airway inflammation in naive mice. We tested the hypothesis that IL-33 is induced by CS and contributes to CS-mediated airway inflammation in a mouse model of CS-induced COPD. Groups of mice were exposed to CS three times per day for 4 consecutive days. The expression levels of IL-33 and ST2 were markedly enhanced in the lung tissue of mice inhaling CS. Exposure to CS also induced neutrophil and macrophage infiltration and expression of inflammatory cytokines ( IL-1β, tumour necrosis factor-α, IL-17), chemokines (monocyte chemoattractant protein-1) and mucin 5, subtypes A and C in the airways. More importantly, all of these CS-induced pathogenic changes were significantly inhibited by treatment with neutralizing anti- IL-33 antibody delivered intranasally. Hence, our results suggest that IL-33 plays a critical role in CS-mediated airway inflammation and may be a therapeutic target in CS-related diseases, including COPD. [ABSTRACT FROM AUTHOR]

Abstract: Toll-like receptors (TLRs) form a family of pattern recognition receptors with at least 11 members in human and 13 in mouse. TLRs recognize a wide variety of putative host-derived agonists that have emerged as key mediators of innate immunity. TLR signaling also plays an important role in the activation of the adaptive immune system by inducing pro-inflammatory cytokines and upregulating costimulatory molecules of antigen presenting cells. Inappropriate activation of TLRs by self-components generated by damaged tissues may result in sterile inflammation. This review discusses the contribution of TLR signaling to the initiation and progression of non-infectious inflammatory processes, such as ischemia and reperfusion (I/R) injury, tissue repair and regeneration and autoimmune diseases. The involvement of TLR signaling in the pathogenesis of sterile inflammation-related diseases may provide novel targets for the development of therapeutics. [Copyright &y& Elsevier]

Abstract: Interleukin (IL)-33 is a recently described member of the IL-1 family and has been shown to induce production of T helper type 2 cytokines. In this study, an anti-IL-33 antibody was evaluated against pulmonary inflammation in mice sensitized and challenged with ovalbumin. The anti-IL-33 or a control antibody (150μg/mouse) was given intraperitoneally as five doses before the sensitization and antigen challenge. Treatment with anti-IL-33 significantly reduced serum IgE secretion, the numbers of eosinophils and lymphocytes, and concentrations of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid compared with administration of a control antibody. Histological examination of lung tissue demonstrated that anti-IL-33 significantly inhibited allergen-induced lung eosinophilic inflammation and mucus hypersecretion. Our data demonstrate for the first time that anti-IL-33 antibody can prevent the development of asthma in a mouse model and indicate that blockade of IL-33 may be a new therapeutic strategy for allergic asthma. [Copyright &y& Elsevier]

• Serum interleukin-38 expression levels were significantly reduced in patients with hyperuricemia. • Serum interleukin-38 was an independent risk factor for hyperuricemia. • Serum interleukin-38 contributed to the clinical diagnosis and risk prediction of hyperuricemia. Interleukin (IL)-38, a novel anti-inflammatory cytokine in the IL-1 family, has an important role in various autoimmune/inflammatory diseases. However, the level of serum IL-38 in hyperuricemia (HUA) and its clinical applications are still unknown. Forty-four HUA patients and 43 healthy controls were enrolled in this study. The levels of serum IL-38 in the participants were detected by enzyme-linked immunosorbent assay. Multivariable logistic regression analysis was used to identify independent risk factors associated with HUA. The least absolute shrinkage and selection operator combined with 10-fold cross-validation was used to screen the characteristic variables for modeling and the logistic regression model was visualized by nomogram. The discrimination, degree of concordance, and clinical applicability of the models were evaluated by receiver operator characteristic curve, calibration plot, and decision curve analysis, respectively. Compared with that in healthy controls, the level of serum IL-38 was reduced in HUA patients (275.09 ± 294.89 vs 505.99 ± 312.94, P < 0.01). The area under the curve of serum IL-38 was 0.768 (cutoff value: 246.91 pg/ml). IL-38, platelet count, mean platelet volume, and total protein were identified as independent risk factors for HUA. The risk model showed an excellent clinical differentiation value (area under the curve: 0.961) and degree of fit. Decision curve analysis indicated that the prediction model could be beneficial for patients when the threshold probability was 1%–95%. Low level of serum IL-38 shows some potential in the clinical diagnosis and risk prediction of HUA. In addition, as a novel biomarker of HUA, serum IL-38 would contribute to the in-depth study of its pathogenesis in the future. [ABSTRACT FROM AUTHOR]