Your browser doesn't support javascript.
Interleukin-38 ameliorates poly(I:C) induced lung inflammation: therapeutic implications in respiratory viral infections.
Gao, Xun; Chan, Paul Kay Sheung; Lui, Grace Chung Yan; Hui, David Shu Cheong; Chu, Ida Miu-Ting; Sun, Xiaoyu; Tsang, Miranda Sin-Man; Chan, Ben Chung Lap; Lam, Christopher Wai-Kei; Wong, Chun-Kwok.
  • Gao X; Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China.
  • Chan PKS; Department of Microbiology, The Chinese University of Hong Kong, Hong Kong, China.
  • Lui GCY; Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong, China.
  • Hui DSC; Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong, China.
  • Chu IM; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
  • Sun X; Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong, China.
  • Tsang MS; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
  • Chan BCL; Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China.
  • Lam CW; Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China.
  • Wong CK; Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China.
Cell Death Dis ; 12(1): 53, 2021 01 07.
Article in English | MEDLINE | ID: covidwho-1015001
ABSTRACT
Interleukin-38 has recently been shown to have anti-inflammatory properties in lung inflammatory diseases. However, the effects of IL-38 in viral pneumonia remains unknown. In the present study, we demonstrate that circulating IL-38 concentrations together with IL-36α increased significantly in influenza and COVID-19 patients, and the level of IL-38 and IL-36α correlated negatively and positively with disease severity and inflammation, respectively. In the co-cultured human respiratory epithelial cells with macrophages to mimic lung microenvironment in vitro, IL-38 was able to alleviate inflammatory responses by inhibiting poly(IC)-induced overproduction of pro-inflammatory cytokines and chemokines through intracellular STAT1, STAT3, p38 MAPK, ERK1/2, MEK, and NF-κB signaling pathways. Intriguingly, transcriptomic profiling revealed that IL-38 targeted genes were associated with the host innate immune response to virus. We also found that IL-38 counteracts the biological processes induced by IL-36α in the co-culture. Furthermore, the administration of recombinant IL-38 could mitigate poly IC-induced lung injury, with reduced early accumulation of neutrophils and macrophages in bronchoalveolar lavage fluid, activation of lymphocytes, production of pro-inflammatory cytokines and chemokines and permeability of the alveolar-epithelial barrier. Taken together, our study indicates that IL-38 plays a crucial role in protection from exaggerated pulmonary inflammation during poly(IC)-induced pneumonia, thereby providing the basis of a novel therapeutic target for respiratory viral infections.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia / Respiratory System / Interleukins / Poly I-C / Influenza, Human / COVID-19 / Immunity, Innate Type of study: Prognostic study Limits: Animals / Humans / Male Language: English Journal: Cell Death Dis Year: 2021 Document Type: Article Affiliation country: S41419-020-03283-2

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia / Respiratory System / Interleukins / Poly I-C / Influenza, Human / COVID-19 / Immunity, Innate Type of study: Prognostic study Limits: Animals / Humans / Male Language: English Journal: Cell Death Dis Year: 2021 Document Type: Article Affiliation country: S41419-020-03283-2