Tumor necrosis factor‑α‑induced protein‑8 like 2 regulates lipopolysaccharide‑induced rat rheumatoid arthritis immune 
responses and is associated with Rac activation and interferon regulatory factor 3 phosphorylation

Shi,Chunyan; Wang,Yue; Zhuang,Guohong; Qi,Zhongquan; Li,Yanping; Yin,Ping

doi:10.3892/mmr.2017.7311

Tumor necrosis factor‑α‑induced protein‑8 like 2 regulates lipopolysaccharide‑induced rat rheumatoid arthritis immune responses and is associated with Rac activation and interferon regulatory factor 3 phosphorylation

Authors:
- Chunyan Shi
- Yue Wang
- Guohong Zhuang
- Zhongquan Qi
- Yanping Li
- Ping Yin
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Affiliations: Organ Transplantation Institute, Anti‑Cancer Research Center, Medical College, Xiamen University, Xiamen, Fujian 361100, P.R. China, Department of Pathology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian 361100, P.R. China
Published online on: August 22, 2017 https://doi.org/10.3892/mmr.2017.7311
Pages: 6346-6353

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Abstract

The endogenously activated rheumatoid arthritis (RA) synovial fibroblasts (RSFs) are likely to be the key to curing the disease. RSFs express Toll‑like receptors (TLRs) rendering them prone to activation by exogenous and endogenous TLR ligands, resulting in the production of chemokines and cytokines Germline deletion of tumor necrosis factor‑α‑induced protein‑8 like 2 (TIPE2, also known as TNFAIP8L2) results in fatal inflammation and hypersensitivity to TLR and T cell receptor stimulation. The present study demonstrates an inverse association between TIPE2 and cytokine gene expression in RSFs following lipopolysaccharide (LPS) stimulation. Enhanced TIPE2 expression decreased Ras‑related C3 botulinum toxin substrate (Rac) activation and interferon regulatory factor 3 phosphorylation, and phosphoinositide 3‑kinase and Rac inhibition significantly diminished LPS‑induced cytokine gene expression in RSFs. In conclusion, the findings of the present study demonstrate that TIPE2 serves a negative role in activating the Rac signaling pathway and in the initiation of the immune response by decreasing the activity of proinflammatory cytokines. These results may be useful in designing novel strategies for the prevention and treatment of RA.

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