IL‑27 suppresses airway inflammation, hyperresponsiveness and remodeling via the STAT1 and STAT3 pathways in mice with allergic asthma

Abstract

Type 2 cytokine-associated immunity may be involved in the pathogenesis of allergic asthma. Although interleukin 27 (IL-27) has been reported as an initiator and suppressor of T-helper 1 (Th1) and T-helper 2 (Th2) responses, respectively, its effects on the development of asthma remain unclear. In the present study, mice were induced and challenged with ovalbumin and received subsequent intranasal administration of IL-27. Total and differential cell counts were determined from Wright-Giemsa-stained cytospins, whereas the cytokine levels were detected using ELISA. In addition, the expression levels of signal transducer and activator of transcription (STAT) 1, STAT3, GATA-binding protein-3 (GATA3) and T-bet (T-box transcription factor) were analyzed in T cells by western blot analysis. Their corresponding mRNA expression levels were determined by quantitative PcR. Airway remodeling was assessed by conventional pathological techniques. The results indicated that intranasal administration of IL-27 ameliorated airway inflammation and hyperresponsiveness in an acute model of asthma. Furthermore, IL-27 prevented airway remodeling in a chronic model of asthma. Following administration of IL-27, the mRNA expression levels of STAT1 and T-bet were upregulated, while those of GATA3 were downregulated. Moreover, the phosphorylation levels of STAT1 and STAT3 were increased. Taken together, these findings demonstrated that intranasal administration of IL-27 ameliorated Th2-related allergic lung inflammation and remodeling in mouse models of asthma by repairing both the STAT1 and STAT3 pathways.

The Role of T Cells and Macrophages in Asthma Pathogenesis: A New Perspective on Mutual Crosstalk

“…In the presence of retinoic acid, AM-associated TGF- β develops Treg cell differentiation [ 112 ]. Lu et al [ 113 ] explained that the anti-inflammatory function of IL-27 from M1 macrophages relied on its suppression of Th2-type inflammation via the STAT1 and STAT3 pathways.…”

In Silico Bioinformatics Followed by Molecular Validation Using Archival FFPE Tissue Biopsies Identifies a Panel of Transcripts Associated with Severe Asthma and Lung Cancer

“…STAT1 is a known transcription factor with roles in both asthma and lung cancer pathogenesis. STAT1 is activated by IL-4, IL-13, and IFNγ and forms either a homodimer or a heterodimer with other STAT proteins to induce the expression of genes related to apoptosis and immune-suppressive cytokines [ 43 , 44 , 45 ]. Among the STATs, STAT1 mRNA expression was observed to be high in NSCLC compared to normal tissue [ 46 ], and it is known to exhibit antitumor activity.…”

Potential Contribution of IL-27 and IL-23 Gene Polymorphisms to Multiple Sclerosis Susceptibility: An Association Analysis at Genotype and Haplotype Level

“…IL-27 activates multiple signaling cascades, such as tyrosine kinase-2, JAK1 and JAK2 [ 28 , 29 ]. IL-27 is involved in the regulation of T helper cells, dendritic cells and macrophages through STAT1 and STAT3 pathways [ 28 ].…”

“…IL-27 activates multiple signaling cascades, such as tyrosine kinase-2, JAK1 and JAK2 [ 28 , 29 ]. IL-27 is involved in the regulation of T helper cells, dendritic cells and macrophages through STAT1 and STAT3 pathways [ 28 ]. IL-27 suppresses T-helper 2 (Th2) production and Th17 differentiation and stimulates T-helper 1 (Th1) cell differentiation through STAT1 pathway [ 30 ].…”

“…In contrast, STAT3 pathway activation plays an important role in Th17 cell differentiation, promoting and increasing IL-17 gene transcription [ 31 ]. In order to maintain an appropriate immune response, the activation of STAT3 works as a counterbalance to activation of STAT1 pathway [ 28 ].…”