Abstract:
:Inter-α-trypsin inhibitors are protease inhibitors that are thought to be important regulators in various acute-phase processes. They are composed of one light chain (bikunin) and different heavy chains (ITIHs). The only function known so far of ITIHs is the covalent linkage to hyaluronan (HA). As there is virtually no knowledge on the distribution and function of ITIH proteins in skin tissue, we performed a systematic characterization of ITIH expression in healthy and diseased skin. Using GeneChip(®) Human Exon 1.0 ST expression profiling, we found that ITIH5 represents the major ITIH family member expressed in human skin. Moreover, the use of quantitative reverse transcription PCR and a customized ITIH5-specific antibody indicated that ITIH5 is predominantly produced by dermal fibroblasts. Immunohistochemical analysis revealed a clearly detectable ITIH5 protein expression in normal skin. Interestingly, ITIH5 expression was significantly up-regulated in inflammatory skin diseases. Furthermore, 3D skin models employing murine Itih5(-/-) epidermal keratinocytes and dermal fibroblasts as well as skin specimens of Itih5(-/-) mice revealed a significantly altered epidermal structure compared to wild-type controls. Hence, we can strengthen the presumption that ITIH5 may constitute a novel regulatory molecule of the human skin that could play an important role in inflammation via its interaction with HA.
journal_name
Exp Dermatoljournal_title
Experimental dermatologyauthors
Huth S,Heise R,Vetter-Kauczok CS,Skazik C,Marquardt Y,Czaja K,Knüchel R,Merk HF,Dahl E,Baron JMdoi
10.1111/exd.12704subject
Has Abstractpub_date
2015-09-01 00:00:00pages
663-8issue
9eissn
0906-6705issn
1600-0625journal_volume
24pub_type
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