Heme oxygenase‐1 alleviates eosinophilic inflammation by inhibiting STAT3‐SOCS3 signaling. Issue 6 (16th April 2020)

• Record Type: Journal Article
• Authors: Lin, Xiaoliang; Lv, Jiajia; Ge, Dandan; Bai, Haitao; Yang, Yungang; Wu, Jinzhun
• Is Part Of: Pediatric pulmonology. Volume 55:Issue 6(2020)
• Page Start: 1440
• Page End: 1447
• Publication Date: 2020-04-16
• Subjects: eosinophilic asthma -- heme oxygenase‐1 -- SOCS3 -- STAT3 -- type 2 immune responses; Pediatric respiratory diseases -- Periodicals; Pediatrics -- Periodicals; 618.922
• DOI: 10.1002/ppul.24759
• Languages: English
• ISSNs: 8755-6863

Abstract

Abstract: Airway inflammation of eosinophilic asthma (EA) attributes to Th2 response, leaving the role of Th17 response unknown. Signal transducer and activator of transcription 3 (STAT3) induce both suppressors of cytokine signaling 3 (SOCS3) and retinoic acid receptor‐related orphan nuclear receptor γ (RORγt) to initiate Th17 cell differentiation which is inhibited by SOCS3, a negative feedback regulator of STAT3. Heme oxygenase‐1 (HO‐1) is a stress‐responsive, cytoprotective, and immunoregulatory molecular. Two other isoforms of the enzyme includes HO‐2 and HO‐3. Because HO‐2 does not exhibit stress‐related upregulation and distributes mainly in nervous system and HO‐3 shows a low enzymatic activity, we tested a hypothesized anti‐inflammatory role for HO‐1 in EA by inhibiting STAT3‐SOCS3 signaling. Animal model was established with Ovalbumin in wild type Balb/C mice. Hemin or SNPP was intraperitoneally (IP) injected ahead of the animal model to induce or inhibit HO‐1 expression. Airway inflammation was evaluated by bronchoalveolar lavage, hematoxyline and eosin staining, enzyme‐linked immunosorbent assay, and Western blot analysis. In vivo results showed that HO‐1 induction inhibited phosphorylation of STAT3 and expression of SOCS3 and RORγt, decreased Th2 and Th17 immune responses, and alleviated airway inflammation. In vitro results revealed that HO‐1 inhibited phosphorylation of STAT3 and expression of SOCS3 in naive CD4 + T cells. These findings identify HO‐1 induction as a potential therapeutic strategy for EA treatment by reducing STAT3 phosphorylation, STAT3‐SOCS3‐mediated Th2/Th17 immune responses, and ultimate allergic airway inflammation.