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Heme oxygenase‐1 inhibits T cell‐dependent skin inflammation and differentiation and function of antigen‐presenting cells
Author(s) -
Listopad Joanna,
Asadullah Khusru,
Sievers Claudia,
Ritter Thomas,
Meisel Christian,
Sabat Robert,
Döcke WolfDietrich
Publication year - 2007
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2007.00581.x
Subject(s) - copp , heme oxygenase , inflammation , immunology , tumor necrosis factor alpha , cytokine , medicine , chemistry , heme , biochemistry , enzyme
Heme oxygenase‐1 (HO‐1) is increased in psoriatic skin. We asked for the impact of physiological and pharmacological HO‐1 induction on skin immunity and the mechanisms involved in HO‐1‐induced immunomodulation. We found cutaneous HO‐1 expression upregulated comparable with suppressors of cytokine signalling (SOCS)1 and SOCS3 in psoriasis and atopic eczema and temporarily increased in murine ovalbumin‐induced late phase reaction (LPR) and 2,4‐dinitrofluorobenzene (DNFB)‐induced contact hypersensitivity (CHS). Cutaneous inflammation was enhanced by HO‐1 inhibition and was abrogated by treatment with the HO‐1 inducer cobaltic protoporphyrin (CoPP) both when applied around sensitization or before challenge. HO‐1 inhibition specifically prevented the anti‐inflammatory CoPP effect. CoPP inhibited T cell proliferation in splenocytes of treated mice and in human mixed leukocyte reaction and lymphocyte transformation test. CoPP induced HO‐1 in antigen‐presenting cells and depressed monocytic accessory molecule expression and the differentiation and maturation of monocyte‐derived dendritic cells (MDDC). It decreased tumor necrosis factor (TNF)‐α and interleukin (IL)‐12 production while increasing IL‐10 secretion. The antigen‐presenting capacity was diminished in CoPP‐treated and HO‐1‐transduced MDDC. We demonstrate for the first time the physiological role of HO‐1 in the limitation of skin inflammation and implement pharmacological HO‐1 induction as a therapeutic approach for T cell‐dependent inflammatory dermatoses. Suppression of antigen‐presenting cells may represent a main anti‐inflammatory mechanism of HO‐1.