Interaction of high-mobility group box 1-activated eosinophils with dermal fibroblasts: implication of damaging inflammation in atopic dermatitis
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摘要Atopic dermatitis (AD) is a widely prevalent inflammatory skin disease. A skin-lesion-related
damage-associated molecular pattern (DAMP) high mobility group box 1 (HMGB1) is DNAbinding
nuclear cytokine in allergic diseases, through binding to the receptor for advanced
glycation end products (RAGE). We evaluate the plasma concentration of HMGB1 in AD
paediatric patients and control subjects using ELISA. In vitro co-culture of primary human
peripheral blood eosinophils and dermal fibroblasts together with AD mice model were used
to elucidate the cellular mechanisms of HMGB1-mediated damaging inflammation in AD.
Significantly elevated plasma concentration of HMGB1 was shown in AD patients when
compared to sex- and age-matched normal control subjects (p = 0.0003). Using MC903-
induced AD-like mouse model, both eosinophils and basophils, the principal effector cells in
allergic inflammation, have been found to infiltrate into the dermal layer. The i.p. injection of
depleting antibodies MAR-1 and TRFK5 drastically eliminated circulating basophils and
eosinophils, respectively and subsequently reduced the induced increment of ear thicknesses
in AD mice. The i.p. injection of anti-HMGB1 antibody alleviated the MC903-induced AD-like
symptoms. HMGB1 could induce the dose-dependent in vitro release of IL-6 and chemokine
CXCL8 and CCL4 from eosinophils and co-culture of eosinophils and dermal fibroblasts. Coculture
exhibited a synergistic induction of AD-related inflammatory IL-6 upon HMGB1
activation compared to eosinophils and dermal fibroblasts alone. HMGB1 could activate the
intracellular nuclear factor (NF)-kB pathway in eosinophils of co-culture with dermal fibroblasts.
Inhibitor for p38 mitogen-activated protein kinase and NF-kB could significantly suppress
HMGB1-mediated AD-related cytokine and chemokine production in the co-culture of
eosinophils and dermal fibroblasts (all p < 0.05). Together, the above clinical, in vitro and
animal result have confirmed HMGB1 is the novel and crucial DAMP molecule linking the
tissue-damage-mediated innate immune response with the subsequent allergic inflammation
through the activation of eosinophils/basophils and dermal fibroblasts.
著者CK Wong, IMT Chu, D Jiao, MSM Tsang, J Zhu, CWK Lam
會議名稱Hong Kong Immunology Forum 2018
會議開始日15.09.2018
會議完結日15.09.2018
會議地點Hong Kong
會議國家/地區香港
出版年份2018
月份9
語言英式英語

上次更新時間 2020-22-04 於 10:08