Interaction of high-mobility group box 1-mediated activation of eosinophils with dermal fibroblasts: implication of damaging inflammation in atopic dermatitis
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摘要Background: 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 a DNA-binding cytokine that can be released passively during cell necrosis, to
induce inflammatory reaction through binding to the receptor for advanced glycation end
products (RAGE).
Methodology: The plasma concentration of HMGB1 in AD patients and control subjects was
measured using ELISA. Co-culture of eosinophils and dermal fibroblasts together with AD
mice model were used to elucidate the damaging inflammatory mechanism mediated by
HMGB1 in AD.
Results: Significantly elevated plasma concentration of HMGB1 was demonstrated in AD
patients (p = 0.0003), and RAGE expression was confirmed on eosinophils/ basophils. The
i.p. injection of depleting antibodies MAR-1 and TRFK5 drastically eliminated circulating
basophils/eosinophils, respectively and subsequently reduced the induced increment of ear
thicknesses in MC903-induced AD mice. Anti-HMGB1 antibody alleviated the AD-like
symptoms in mice. HMGB1 could induce the dose-dependent release of IL-6 and chemokine
CXCL8 and CCL4 from eosinophils and co-culture of eosinophils-dermal fibroblasts.
HMGB1 could activate the intracellular nuclear factor (NF)-��B 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/chemokine
production in co-culture of eosinophils and dermal fibroblasts (all p < 0.05).
Conclusion: The above results 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 and dermal fibroblasts, via
distinct intracellular signaling mechanisms in AD.
著者CK WONG, IMT CHU, D JIAO, MSM TSANG, J ZHU, CWK LAM
會議名稱24th Annual Scientific Meeting, Hong Kong Society of Flow Cytometry
會議開始日09.03.2019
會議完結日09.03.2019
會議地點Hong Kong
會議國家/地區香港
出版年份2019
月份3
語言英式英語

上次更新時間 2020-22-04 於 10:14