Abstract
The regulatory role of suppressor of cytokine signaling 1 (SOCS1) in inflammation has been reported. However, its role in allergic inflammation has not been previously reported. SOCS1 mediated in vitro and in vivo allergic inflammation. Histone deacetylase-3 (HDAC3), a mediator of allergic inflammation, interacted with SOCS1, and miR-384 inhibitor, a positive regulator of HDAC3, induced features of allergic inflammation in an SOCS1-dependent manner. miRNA array analysis showed that the expression of miR-122 was decreased by antigen-stimulation. TargetScan analysis predicted the binding of miR-122 to the 3′-UTR of SOCS1. miR-122 inhibitor induced in vitro and in vivo allergic features in SOCS1-dependent manner. SOCS1 was necessary for allergic inflammation-promoted enhanced tumorigenic and metastatic potential of cancer cells. SOCS1 and miR-122 regulated cellular interactions involving cancer cells, mast cells and macrophages during allergic inflammation. SOCS1 mimetic peptide, D-T-H-F-R-T-F-R-S-H-S-D-Y-R-R-I, inhibited in vitro and in vivo allergic inflammation, allergic inflammation-promoted enhanced tumorigenic and metastatic potential of cancer cells, and cellular interactions during allergic inflammation. Janus kinase 2 (JAK2) exhibited binding to SOCS1 mimetic peptide and mediated allergic inflammation. Transforming growth factor- Δ1 (TGF-Δ1) was decreased during allergic inflammation and showed an anti-allergic effect. SOCS1 and JAK2 regulated the production of anti-allergic TGF-Δ1. Taken together, our results show that miR-122-SOCS1 feedback loop can be employed as a target for the development of anti-allergic and anti-cancer drugs.
Highlights
suppressor of cytokine signaling 1 (SOCS1) inhibits excessive cytokine signaling, based on the fact that SOCS1-knockout (KO) mice die of severe inflammation within three weeks of birth [1]
These results suggest the role of SOCS1 in allergic inflammation
The conditioned medium of antigen-stimulated RBL2H3 cells obtained in www.impactjournals.com/oncotarget the absence of treatment with SOCS1-KIR, when added to B16F1 cells, enhanced the invasion and migration potential of B16F1 cells (Figure 10G). These results suggest that SOCS1 mediates the interaction between cancer cells and mast cells during allergic inflammationpromoted enhanced tumorigenic and metastatic potential
Summary
SOCS1 inhibits excessive cytokine signaling, based on the fact that SOCS1-knockout (KO) mice die of severe inflammation within three weeks of birth [1]. SOCS1 decreases IL-6 production in LPS-stimulated RAW 264.7 cells [2]. Secretory SOCS1 exerts anti-inflammatory effects [3]. Neuroprotective and anti-inflamamtory effects of resveratrol result from the induction of SOCS1 [4]. Carvedilol reduces oxidative stress, inflammatory response and fibrosis in ethanol-induced liver injury in a rat model by induction of SOCS1 and suppression of inflammatory www.impactjournals.com/oncotarget cytokines [5]. Olmesartan exerts an anti-inflammatory effect by upregulating SOCS1 [6]. Goat whey exerts a preventive effect against intestinal damage induced by acetic acid by upregulating SOCS1 [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
