Macrophage-derived heme-oxygenase-1:: Expression, regulation, and possible functions in skin repair

被引：33

作者：

Kämpfer, H ^{[1
]}

Kolb, N ^{[1
]}

Manderscheid, M ^{[1
]}

Wetzler, C ^{[1
]}

Pfeilschifter, J ^{[1
]}

Frank, S ^{[1
]}

机构：

[1] Univ Frankfurt Klinikum, Pharmazentrum Frankfurt, Inst Allgemeine Pharmakol & Toxikol, D-60590 Frankfurt, Germany

来源：

MOLECULAR MEDICINE | 2001年 / 7卷 / 07期

关键词：

D O I：

10.1007/BF03401854

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Background: Expression and enzymatic activity of heme oxygenase (HO) has been implicated in the development, as well as in the resolution, of inflammatory conditions. Because inflammation is central to tissue repair, we investigated the presence and potential functions of HO in an excisional model of normal and diabetes-impaired wound repair in mice. Materials and Methods: Expression of HO-1 during cutaneous healing was analyzed by RNase protection assay, Western blot, and immunohistochemical techniques in a murine model of excisional repair. Furthermore, we determined HO-1-dependent release of proinflammatory cytokines from RAW 264.7 macrophages by enzyme-linked immunosorbent assay (ELISA). Results: Upon injury, we observed a rapid and strong increase in HO-1 mRNA and protein levels at the wound site. By contrast to normal repair, late stages of diabetes-impaired repair were associated with elevated HO-1 expression. Besides a few keratinocytes of the hyperpro-liferative epithelium, immunohistochemistry revealed infiltrating macrophages as the predominant and major source of HO-1 at the wound site. in vitro studies demonstrated the potency of exogenous and also endogenous nitric oxide (NO) to strongly induce HO-1 expression in RAW 264.7 macrophages. However, L-NIL-mediated enzymatic inhibition of inducible NO-synthase (iNOS) at the wound site in vivo was not paralleled by decreased HO-1 levels. In vitro inhibition of HO-1 enzymatic activity by tin protoporphyrin IX (SnPPIX) in RAW 264.7 macrophages markedly attenuated tumor necrosis factor-alpha (TNF-alpha), but strongly increased interleukin-1 beta (IL-1 beta) release in RAW 264.7 macrophages in vitro. Conclusions: The observed injury-mediated increase in HO-1 mRNA and protein at the wound site was due to infiltrating HO-1 expressing monocytic cells. Macrophage-derived HO-1 expression was not under regulatory control by NO in skin repair. We provide evidence that HO-1 might exert a regulatory role in macrophage-derived cytokine release.

引用

页码：488 / 498

页数：11

共 62 条

[1] TRANSFECTION OF THE HUMAN HEME OXYGENASE GENE INTO RABBIT CORONARY MICROVESSEL ENDOTHELIAL-CELLS - PROTECTIVE EFFECT AGAINST HEME AND HEMOGLOBIN TOXICITY [J].