Upregulation of chemokine CXCL10 enhances chronic pulmonary inflammation in tree shrew collagen-induced arthritis

  • Sci Rep. 2018 Jul 3;8(1):9993. doi: 10.1038/s41598-018-28404-y.
Bo Gao  1  2 ,  Jie Lin  2  3 ,  Zongmin Jiang  1  2 ,  Zhongshan Yang  4 ,  Haijing Yu  1  2 ,  Lei Ding  1  2 ,  Min Yu  1  2 ,  Qinhua Cui  1  2 ,  Neil Dunavin  5 ,  Ming Zhang  6 ,  Meizhang Li  7  8
Affiliations
  • 1. Lab of Biochemistry & Molecular Biology, School of Life Sciences, Yunnan University, Kunming, Yunnan, 650091, China.
  • 2. Key Lab of Molecular Cancer Biology, Yunnan Education Department, Kunming, Yunnan, 650091, China.
  • 3. Lab of Monoclonal Antibody Engineering &Technology, School of Life Sciences, Yunnan University, Kunming, Yunnan, 650091, China.
  • 4. Lab of Pathogen Biology and Immunology, Yunnan Traditional Chinese Medicine University, Kunming, Yunnan, 650500, China.
  • 5. Division of Hematologic Malignancies and Cellular Therapeutics, Kansas University Medical Center, KS, 66205, USA.
  • 6. Yunnan Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, Yunnan, 650500, China. [email protected].
  • 7. Lab of Biochemistry & Molecular Biology, School of Life Sciences, Yunnan University, Kunming, Yunnan, 650091, China. [email protected].
  • 8. Key Lab of Molecular Cancer Biology, Yunnan Education Department, Kunming, Yunnan, 650091, China. [email protected].
PMID: 29968810 DOI: 10.1038/s41598-018-28404-y
Abstract

Chronic pulmonary inflammation (CPI) gives rise to serious lung injuries in rheumatoid arthritis (RA) patients. However, the molecular mechanism underlying the pathogenesis of RA-associated CPI remains little understood. Here we established a novel tree shrew-based collagen-induced arthritis (TsCIA) model to study RA-associated CPI. Our results showed that typical CPI but not fibrosis developed pathologically in the TsCIA model. Furthermore, abnormal up-regulation of pulmonary chemokine CXCL10 was directly associated with lung damage. Specific blockage of CXCR3 (a CXCL10 receptor) significantly decreased the severity of CPI by decreasing the recruitment of inflammatory cells. Therefore, CXCL10 is proposed as a key player responsible for the development of TsCIA-associated CPI. Our findings also suggest that CXCR3 could be developed as a potential diagnosis biomarker for RA-associated CPI.

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