Targeting of interleukin-10 receptor by a potential human interleukin-10 peptide efficiently blocks interleukin-10 pathway-dependent cell proliferation

Chun-Chun Chang; Cheng-Der Liu; Sheng-Feng Pan; Wei-Han Huang; Chih-Wen Peng; Hao-Jen Hsu

doi:10.4103/tcmj.tcmj_237_19

Targeting of interleukin-10 receptor by a potential human interleukin-10 peptide efficiently blocks interleukin-10 pathway-dependent cell proliferation

Ci Ji Yi Xue Za Zhi. 2020 Jan 17;32(3):245-253. doi: 10.4103/tcmj.tcmj_237_19. eCollection 2020 Jul-Sep.

Authors

Chun-Chun Chang¹, Cheng-Der Liu², Sheng-Feng Pan³, Wei-Han Huang⁴, Chih-Wen Peng², Hao-Jen Hsu^{3

5}

Affiliations

¹ Department of Laboratory Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
² Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.
³ Department of Biochemistry, School of Medicine, Tzu Chi University, Hualien, Taiwan.
⁴ Department of Oncology and Hematology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
⁵ Department of Life Sciences, Tzu Chi University, Hualien, Taiwan.

Abstract

Objective: Human interleukin-10 (IL-10) is a dimeric and pleiotropic cytokine that plays a crucial role in cellular immunoregulatory responses. As IL-10 binds to its receptors, IL-10Ra and IL-10Rb, it will suppress or induce the downstream cellular immune responses to protect from diseases.

Materials and methods: In this study, a potential peptide derived from IL-10 based on molecular docking and structural analysis was designed and validated by a series of cell assays to block IL-10 binding to receptor IL-10Ra for the inhibition of cell growth.

Results: The simulation results indicate that the designed peptide IL10NM25 bound to receptor IL-10Ra is dominated by electrostatic interactions, whereas van der Waals (VDW) and hydrophobic interactions are minor. The cell experiments showed that IL10NM25 specifically binds to receptor IL-10Ra on the cell surface of two B-lineage cell lines, B lymphoma derived (BJAB), and lymphoblastoid cell line, whereas the mutant and scramble peptides are not able to suppress the binding of IL-10 to receptor IL-10Ra, consistent with the molecular simulation predictions.

Conclusion: This study demonstrates that structure-based peptide design can be effective in the development of peptide drug discovery.

Keywords: Cytokine; Interleukin-10; Molecular docking; Peptide design.