stat1

Tobacco use is responsible for millions of preventable deaths due to cancer. Nicotine, an alkaloid chemical found in tobacco was proved to cause chronic inflammation and oxidative stress. The transcription factor STAT1 induces the expression of many proinflammatory genes and has been suggested to be a target for anti-inflammatory therapeutics. The following study investigated the effect of Nicotine on STAT1 pathway and oxidative stress in rat lung tissue. 

Thirty rats were divided into 3 groups; group I considered as control, group II; its rats were daily injected with Nicotine at a dose of 0.4 mg/100 gm body for 8 successive weeks and group III; its rats were daily injected with Nicotine as group II, but the injection was stopped for another 4
weeks. STAT1α protein was assessed by immunohistochemistry, COX-2 and iNOS genes expression were evaluated by real time PCR and thiobarbituric acid reactive substances (TBARS) and total thiols were measured using spectrophotometric methods in the lung tissues of the rats.

The results of the study revealed that group II rats had the highest expression of STAT1α protein and COX-2 and iNOS genes and oxidative stress in their lung tissues. Nicotine cessation for 4 weeks caused a marked reduction in the expression of STAT1α protein, COX-2 and iNOS genes and oxidative stress.

Induction of STAT1 pathway and the increase in oxidative stress may be the mechanisms through which Nicotine may induce its harmful effects.

The critical role of IFN signature genes has increasingly been surveyed to determine the etiology and pathogenesis of systemicsclerosis (SSc). Interferon-regulatory factors (IRFs) and signal transducers and activators of transcription (STATs) are mainlyconsidered as transcriptional modulators of IFN-signature genes and type I interferon and play a major role in the regulation ofnumerous aspects of an immune response. The current study aimed to assess the transcriptional levels of IRF7 (interferonregulatory factor 7) and STAT1 (signal transducers and activators of transcription 1) mRNAs in PBMCs of scleroderma patientsand compare them with those of healthy subjects.In this study, PBMCs were obtained from 50 scleroderma patients and 30 healthy individuals. Subsequently, total RNA wasextracted from isolated PBMCs and cDNA synthesis was carried out. IRF7 and STAT1 mRNA expressions were assessed byapplying quantitative real-time PCR, SYBR Green method, and specific primers for IRF7 and STAT1.Relative expression of IRF7 was significantly increased in the patient group compared with the control group. Moreover, relativeexpression of IRF7 in limited SSc (lSSc) and diffuse SSc (dSSc) was significantly increased compared with healthy subjects (p< 0.05). The relative expression of STAT1 transcripts in PBMCs was not statistically significantly different between the patientgroup and the control group. The correlation between IRF7 expression and the Rodnan score (RS) of the disease was significant.Considering the overexpression of IRF7 in SSc patients and significant correlation between the IRF7 and the Rodnan score ofthe disease, it is suggested that impaired expression of IRF7 is involved in the pathogenesis of SSc.

Previously we reported functional leukocyte immunoglobulin-like receptor A3 (LILRA3) leads to susceptibility and sub-phenotypes of several autoimmune diseases. LILRA3 levels in blood serum and CD14+ monocytes enhanced in systemic lupus erythematosus and resulted in disease severity. However, the mechanism of LILRA3 in the pathogenesis of autoimmunity remains elusive. This study aims to explore the potential impact of LILRA3 on the differentiation, maturation, and function of monocyte-derived DCs (MoDCs). The human monocytic cell line (THP-1) was cultured to derive MoDCs in vitro. We performed plasmid transfection to examine the impact of LILRA3 on monocyte differentiation. Surface markers on MoDCs were measured using FACS. To assess the function of mature MoDCs, IL-12p70, IFN-γ and IL-4 levels were detected after the mixed leucocyte response by enzyme-linked immunosorbent assay. Western blot assay was employed in this study to determine the signaling pathways in MoDCs activation. LILRA3 promotes MoDCs maturation, our results showed significant up-regulation of CD40, CD80, CD86, CD209, and HLA-DR and increased production of pro-inflammatory cytokine IL-12. LILRA3-treated MoDCs exhibited a robust proliferation of allogeneic CD4+ T cells and induced naïve CD4+ T cell polarization into the Th1 phenotype. Furthermore, the preceding activation of MoDCs maturation and LILRA3 function might be attributed to p38 MAPK and STAT1 signaling pathway’s aberrant activation. This is the first study to report that LILRA3 played a critical role in promoting MoDCs maturation and directing MoDCs to modulate Th1 cell differentiation, which may have a role in the pathogenesis of autoimmune diseases.