title: Inter-α-trypsin inhibitor heavy chain 5 (ITIH5) is overexpressed in inflammatory skin diseases and affects epidermal morphology in constitutive knockout mice and murine 3D skin models.
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.
authors: Department of Dermatology and Allergology, University Hospital of the RWTH, Aachen, Germany.|Molecular Oncology Group, Institute of Pathology, University Hospital of the RWTH, Aachen, Germany.
authors: Sebastian
authors: S
authors: Huth
authors: Department of Dermatology and Allergology, University Hospital of the RWTH, Aachen, Germany.
authors: Ruth
authors: R
authors: Heise
authors: Department of Dermatology, Julius-Maximilians-University, Würzburg, Germany.
authors: Claudia S
authors: CS
authors: Vetter-Kauczok
authors: Department of Dermatology and Allergology, University Hospital of the RWTH, Aachen, Germany.
authors: Claudia
authors: C
authors: Skazik
authors: Department of Dermatology and Allergology, University Hospital of the RWTH, Aachen, Germany.
authors: Yvonne
authors: Y
authors: Marquardt
authors: Department of Dermatology and Allergology, University Hospital of the RWTH, Aachen, Germany.
authors: Katharina
authors: K
authors: Czaja
authors: Molecular Oncology Group, Institute of Pathology, University Hospital of the RWTH, Aachen, Germany.
authors: Ruth
authors: R
authors: Knüchel
authors: Department of Dermatology and Allergology, University Hospital of the RWTH, Aachen, Germany.
authors: Hans F
authors: HF
authors: Merk
authors: Molecular Oncology Group, Institute of Pathology, University Hospital of the RWTH, Aachen, Germany.
authors: Edgar
authors: E
authors: Dahl
authors: Department of Dermatology and Allergology, University Hospital of the RWTH, Aachen, Germany.
authors: Jens M
authors: JM
authors: Baron
mesh_terms: D000510:Alpha-Globulins / Q000235:genetics; D000818:Animals; D001798:Blood Proteins / Q000235:genetics; D002478:Cells, Cultured; D004817:Epidermis / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005347:Fibroblasts; D015870:Gene Expression; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D007249:Inflammation / Q000235:genetics; D015603:Keratinocytes; D051379:Mice; D018345:Mice, Knockout; D008953:Models, Anatomic; D020411:Oligonucleotide Array Sequence Analysis; D053491:Proteinase Inhibitory Proteins, Secretory / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012871:Skin Diseases / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000510:Alpha-Globulins; D001798:Blood Proteins; D006023:Glycoproteins; C091236:ITIH4 protein, human; C482680:ITIH5 protein, human; C580709:ITIH5 protein, mouse; D053491:Proteinase Inhibitory Proteins, Secretory; D012333:RNA, Messenger; C011877:inter-alpha-inhibitor; D006820:Hyaluronic Acid
keywords: ITIH5; ITIH5 knockout mouse; hyaluronan; inflammatory skin diseases; murine 3D skin model