Pulmonary fibrosis (PF) is the last phase of interstitial lung diseases (ILDs), which are a collection of pulmonary illnesses marked by parenchymal remodeling and scarring. Treatment can only halt the functional decline of the lung, raising the necessity of identifying the basic processes implicated in lung fibrogenesis. The Interferon lambda-3 (IFNL3) gene variant, rs12979860, was determined to be related to an elevated risk of fibrosis in different organs, but the mechanism through which it mediates fibrogenesis is not clear. In the current research, we aim to figure out some of the mechanistic pathways by which IFN-λ3 mediates ILDs. 100 healthy controls and 74 ILD patients were genotyped for IFNL3 rs12979860. Then the mRNA expression of IFNL3 and some other proinflammatory mediators was examined according to genotype in the peripheral blood mononuclear cells (PBMCs) of ILDs patients. The IFNL3 rs12979860 genotype distribution of healthy individuals and ILDs patients was shown to be in Hardy-Weinberg equilibrium (HWE) with a minor allele frequency (MAF) of 0.293 and 0.326, respectively. Furthermore, the CC genotype was demonstrated to be linked to enhanced IFNL3 expression. Also, the CC genotype was linked to an increase in the mRNA expression of TLR4 (P = 0.03) and the inflammatory cytokines IL-1β and TNF-α (P = 0.01 and 0.04, respectively) and had no effect on the NF-kB level (P = 0.3). From these results, we can deduce that IFN-λ3 may mediate tissue fibrosis via increasing the expression of IFN-λ3 itself and other proinflammatory mediators. This stimulates a self-sustaining loop mechanism which includes a reciprocal production of IFN-λ3, TLR4, IL-1β, and TNF-α leading to persistent inflammation and fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial respiratory illness with an unknown origin, which leads to inevitably fatal outcomes in the majority of cases. The pro-inflammatory cytokine interferon lambda-3 (IFN-λ3) has been recently identified as a risk factor for the development of lung fibrosis in scleroderma patients. In this study, we examined the involvement of IFN-λ3 in IPF by utilizing the mouse model of BLM-induced pulmonary fibrosis. Our study identifies a remarkable overexpression in the mRNA of IFNL3, and a positive significant correlation between the IFNL3 mRNA levels and the various pro-inflammatory cytokines for instance NF-kB, TNF-α, IL-1β and TGF-β throughout the three-weeks study. These findings have proven the impact of IFNL3 on BLM-induced pulmonary fibrosis occurrence and progression. Moreover, the data suggest that the pro-inflammatory and pro-fibrotic capacities of IFNL3 may be provoked by additional pro-inflammatory cytokines NF-kB, TNF-α, IL-1β, and TGF-β. In conclusion, IFN-λ3 looks like a promising target in the therapeutic development of new drug candidates for pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial respiratory illness with an unknown origin. that led to inevitably fatal outcomes in the majority of cases. A pro-inflammatory cytokine interferon lambda-3 (IFN-λ3) has been recently identified as risk factor for the development of lung fibrosis in scleroderma patients. In this study we examined the involvement of IFN-λ3 in IPF by utilizing the mice model of BLM-induced pulmonary fibrosis. Our study identifies a remarkable overexpression in the mRNA of IFNL3, and positive significant correlation between the IFNL3 mRNA levels and the various pro-inflammatory cytokines for instance NF-kB, TNF-α, IL-1B and TGF-β over the course of the three-weeks study. These findings have proven the impact of IFNL3 in BLM-induced pulmonary fibrosis occurrence and progression. Moreover, the data suggest that the pro-inflammatory and pro-fibrotic capacities of IFNL3 may be provoked by additional pro-inflammatory cytokines NF-kB, TNF-α, IL-1B, and TGF-β.In conclusion, IFN-λ3 looks like a promising target in the therapeutic development of new drug candidates for pulmonary fibrosis

Thrombocytopenia in chronic hepatitis C patients is a serious complication, which hinders starting and continuation of several invasive diagnoses and treatment protocols. This problem is multifactorial; therefore, it is important to explore host factors linked to it. Interestingly while we were investigating the association between rs58542926 polymorphism in TM6SF2 gene and both hepatic & extra hepatic changes, we found a significant association between TM6SF2 risk allele and thrombocytopenia in Egyptian CHC patients. There are 351 participants in this study. We measured gene expression of IL-6 and TNF-α in PBMCs and plasma thrombopoietin level in 20 CHC patients with advanced fibrosis. The minor allele was linked to elevated thrombocytopenia, and lower thrombopoietin levels. These findings raise concerns regarding the effect of this polymorphism on different diagnostic techniques and the outcomes of HCV treatment. In conclusion, we demonstrated for the first time that the occurrence of the minor allele of the rs58542926 polymorphism is associated not only with hepatic but also with extrahepatic (thrombocytopenia) alterations in CHC Egyptian patients, allowing for the use of this variant as a pharmacogenetic marker to recognize CHC patients who have a high possibility for developing late stages of liver fibrosis and extrahepatic complications.