1. Academic Validation
  2. Conserved structure and function of chemokine CXCL8 between Chinese tree shrews and humans

Conserved structure and function of chemokine CXCL8 between Chinese tree shrews and humans

  • Gene. 2018 Nov 30;677:149-162. doi: 10.1016/j.gene.2018.07.025.
Zongmin Jiang 1 Bo Gao 1 Min Hu 2 Lei Ding 1 Zhenwei Lan 1 Min Yu 1 Haijing Yu 1 Qinghua Cui 1 Jie Lin 3 Meizhang Li 4
Affiliations

Affiliations

  • 1 Laboratory of Biochemistry & Molecular Biology, School of Life Sciences, Yunnan University, Kunming, Yunnan 650091, China; Key Laboratory for Tumor Molecular Biology of High Education in Yunnan Province, School of Life Sciences, Yunnan University, Kunming, Yunnan 650091, China.
  • 2 Kunming Research Center for Molecular Medicine, Kunming University, Kunming, Yunnan 650214, China.
  • 3 Key Laboratory for Tumor Molecular Biology of High Education in Yunnan Province, School of Life Sciences, Yunnan University, Kunming, Yunnan 650091, China; Monoclonal Antibody Engineering & Technology Center, School of Life Sciences, Yunnan University, Kunming, Yunnan 650091, China. Electronic address: [email protected].
  • 4 Laboratory of Biochemistry & Molecular Biology, School of Life Sciences, Yunnan University, Kunming, Yunnan 650091, China; Key Laboratory for Tumor Molecular Biology of High Education in Yunnan Province, School of Life Sciences, Yunnan University, Kunming, Yunnan 650091, China. Electronic address: [email protected].
Abstract

Chemokines represent a superfamily of small secretion proteins that functionally mediate immune cell transmigration in normal or inflammatory conditions. Although anatomic and polygenetic evidence suggests that tree shrews are primate-like species, understanding of the structure and function of tree shrew chemokines has only just commenced. In this study, we cloned tree shrew chemokine CXCL8 and its cognate receptors. Predicted three-dimensional (3D) structures showed that binding domains in CXCL8 and CXCR1/2 were highly conserved between tree shrews and humans. We found that the human CXCL8 (hCXCL8) protein induced migration of tree shrew peripheral blood mononuclear cells (PBMCs) expressed by CXCR1/2 (tsCXCR1/2). Blocking interaction between hCXCL8 and tsCXCR1/2 with allosteric antagonists (reparixin and SB265610) significantly decreased tree shrew PBMC transmigration. Over-expressing tree shrew CXCR1 in human HEK 293 T cells further enhanced cellular in vitro transmigration. Similar to primate species, our findings suggest that CXCL8 and CXCR1/2 constitute a structurally- and functionally-conserved chemotaxis responsible for tree shrew immune activities.

Keywords

CXCL8; CXCR1/2; Chemokine; Transmigration; Tree shrew.

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