Anti-inflammatory Activity of the Novel Cytokine Interleukin-38 in Allergic Asthma
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AbstractBackground: Interleukin (IL)-38 is a newly discovered cytokine and also known as the tenth
member of IL-1 cytokine family. It has been reported that IL-38 displays anti-inflammatory
activity in many diseases including autoimmune diseases. Our study aimed to elucidate the
anti-inflammatory role of IL-38 in allergic asthmatic mice.
Methods: To evaluate the anti-inflammatory activities of IL-38 in vitro, human primary
bronchial epithelial cells (HBEpiC) and eosinophils were co-cultured, and then stimulated
with viral RIG-I-like receptor ligand poly(I:C)/LyoVec or inflammatory tumor necrosis factor
(TNF)-α in the presence of human recombinant IL-38. The culture supernatants were
obtained for the quantification of cytokines and chemokines, and cells were collected for flow
cytometric analysis. In addition, house dust mite (HDM)-induced allergic asthmatic murine
model and HDM-induced humanized asthmatic NOD/SCID murine model were established
to evaluate the in vivo anti-inflammatory role of IL-38.
Results: IL-38 significantly inhibited inflammatory cytokines IL-6 and IL-1β release,
inflammatory chemokines CCL5 and CXCL10 production as well as intercellular adhesion
molecule (ICAM)-1 expression in co-culture system. Mass cytometry analysis revealed that
IL-38 could antagonize the activation of signal transducer and activator of transcription 1
(STAT1), STAT3, STAT5, p38 mitogen-activated protein kinases (MAPK) and extracellular
signal-regulated kinase 1/2 (ERK 1/2) pathways. Moreover, in HDM-induced allergic
asthmatic model, IL-38 intraperitoneal injection could ameliorate airway hyperreactivity in
asthmatic mice through decreasing accumulation of eosinophils in lung, and inhibiting the
expression of T helper (Th)2-related cytokines IL-4, IL-5, and IL-13 in bronchoalveolar
lavage fluid (BALF) and lung homogenates. Histological examination indicated that IL-38
could alleviate lung inflammation by reducing cell infiltration and goblet cell hyperplasia in
mice when compared with asthma group. Also, mice receiving peritoneal injection with IL-38
showed reduced frequencies of Th2 and Th17 cells and increased proportions of Treg cells in
both lung and spleen. The therapeutic potential of IL-38 was further validated in humanized
mouse model. Administration of IL-38 suppressed asthma-related cytokines and chemokines
such as IL-5, IL-6, and CCL5. The injection of IL-38 significantly reduced the number of
eosinophils in the BALF of mice, and the number of human CD4+CRTH2+Th2 cells in the
lung of mice was decreased compared with asthmatic mice.
Conclusion: Taken together, our data demonstrated the anti-inflammatory role of IL-38 in
HBEpiC and human primary eosinophils co-culture system, and further confirmed its antiinflammatory
effect in both allergic asthmatic murine model and humanized model of
asthma.
All Author(s) ListXiaoyu SUN, Tianheng HOU, Jing ZHU, Miranda Sin-Man TSANG, Ida Miu Ting CHU, Helen Yau-Tsz CHAN, Dehua LIU, Chun-Kwok WONG
Name of Conference24th Annual Scientific Meeting, Hong Kong Society of Flow Cytometry
Start Date of Conference09/03/2019
End Date of Conference09/03/2019
Place of ConferenceHong Kong
Country/Region of ConferenceHong Kong
Year2019
Month3
LanguagesEnglish-United Kingdom

Last updated on 2020-22-04 at 10:22