transforming-growth-factor-beta and Dermatomycoses

Jorge Lobo's and chromoblastomycosis are chronic deep mycosis that clinically manifests as keloid and verrucous polymorphic lesions of solid consistency and variable size that contain small scales and crusts. Few studies are available in the literature characterizing the in situ cellular and humoral immune response, especially the involvement of cytokines which immunosuppressive and fibrogenic effects as the TGF-beta. The hypothesis of the present paper is explaining the possible mechanism of this cytokine in cutaneous lesions pathology in chromoblastomycosis and lacaziosis (Jorge Lobo's disease). The results of this investigation are a new hypothesis for ethiopatogenesis of these diseases: TGF-beta is a double effect that follows fibrosis and immunosuppression in local skin.

Topics: Chronic Disease; Dermatomycoses; Humans; Models, Immunological; Skin; Soft Tissue Infections; Subcutaneous Tissue; Transforming Growth Factor beta

Antimicrobial peptides of the beta-defensin family are expressed in all human epithelial tissues tested to date and have recently been the subject of vigorous investigation. Their localization and characteristics support the hypothesis that these peptides play a role in mucosal and skin defense. The lipophilic yeast Malassezia furfur is a saprophyte found in normal human cutaneous flora. Malassezia furfur is not only a saprophyte, but is also associated with several diseases such as Malassezia folliculitis, seborrheic dermatitis and some forms of atopic dermatitis, psoriasis and confluent and reticulate papillomatosis. Little is known about the mechanism by which M. furfur overcomes the natural barrier of the skin. To further define the role of the beta-defensins in the innate human skin immune response, we analyzed the mRNA expression of two human beta-defensins HBD-1 and HBD-2 in human keratinocytes treated with M. furfur. In addition, we looked into how M. furfur of TGF-beta1 and IL-10, cytokines that interfere with the development of protective cell immunity, regulate their expression. Finally, we examined the signal transduction mechanisms involved during M. furfur uptake. Cultured human keratinocytes were treated with M. furfur. The mRNA and protein expression were analyzed, respectively, by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting. Our data demonstrate that M. furfur does not modify HBD-1 expression, whereas it up-regulates, via protein kinase C (PKC), the expression of HBD-2, TGFbeta-1 and IL-10 48 h after treatment. Our results suggest that beta-defensins are integral components of innate host defenses. They play an essential part in the resistance of the human skin surfaces against M. furfur uptake and other microbial invasion.

Topics: beta-Defensins; Cell Division; Cells, Cultured; Dermatomycoses; Gene Expression; Humans; Interleukin-10; Keratinocytes; Malassezia; Protein Kinase C; Signal Transduction; Transcription Factor AP-1; Transforming Growth Factor beta; Transforming Growth Factor beta1