Publications (6)33.2 Total impact
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Article: Transient receptor potential vanilloid-2 mediates the effects of transient heat shock on endocytosis of human monocyte-derived dendritic cells.
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ABSTRACT: Our goal was to investigate the effect of heat shock on human monocyte-derived dendritic cells (DCs) and to dissect the role of thermosensitive transient receptor potential (TRP) in the process. We provide evidence that a short heat shock challenge (43°C) decreased the endocytotic activity of the DCs and that this effect could be alleviated by the RNAi-mediated knockdown of TRPV2 but, importantly, not by the pharmacological (antagonists) or molecular (RNAi) suppression of TRPV1 and TRPV4 activities/levels. Likewise, the heat shock-induced robust membrane currents were selectively and markedly inhibited by TRPV2 "silencing" whereas modulation of TRPV1 and TRPV4 activities, again, had no effect. These intriguing data introduce TRPV2-coupled signaling as a key player in mediating the cellular actions of heat shock on DCs.FEBS letters 03/2013; · 3.54 Impact Factor -
Article: The Channel Physiology of the Skin.
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ABSTRACT: During embryonic development, the skin, the largest organ of the human body, and nervous system are both derived from the neuroectoderm. Consequently, several key factors and mechanisms that influence and control central or peripheral nervous system activities are also present and hence involved in various regulatory mechanisms of the skin. Apparently, this is the case for the ion and non-ion selective channels as well. Therefore, in this review, we shall focus on delineating the regulatory roles of the channels in skin physiology and pathophysiology. First, we introduce key cutaneous functions and major characteristics of the channels in question. Then, we systematically detail the involvement of a multitude of channels in such skin processes (e.g. skin barrier formation, maintenance, and repair, immune mechanisms, exocrine secretion) which are mostly defined by cutaneous non-neuronal cell populations. Finally, we close by summarizing data suggesting that selected channels are also involved in skin diseases such as e.g. atopic dermatitis, psoriasis, non-melanoma cancers and malignant melanoma, genetic and autoimmune diseases, etc., as well as in skin ageing.Ergebnisse der Physiologie 11/2012; · 6.25 Impact Factor -
Article: Protein kinase C isoforms have differential roles in the regulation of human sebocyte biology.
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ABSTRACT: Protein kinase C (PKC) isoforms have crucial roles in cutaneous signaling. Interestingly, we lack information about their involvement in human sebaceous gland biology. Therefore, in this current study, we investigated the functions of the PKC system in human immortalized SZ95 sebocytes. Using molecular biological approaches, imaging, and functional assays, we report that SZ95 sebocytes express the conventional cPKCα; the novel nPKCδ, ɛ, and η; and the atypical aPKCζ. Activation of the PKC system by phorbol 12-myristate 13-acetate (PMA) stimulated lipid synthesis (a hallmark of differentiation) and resulted in translocation and then downregulation of cPKCα and nPKCδ. In good accord with these findings, the effect of PMA was effectively abrogated by inhibitors and short interfering RNA-mediated "silencing" of cPKCα and nPKCδ. Of further importance, molecular or pharmacological inhibition of nPKCδ also prevented the lipogenic and apoptosis-promoting action of arachidonic acid. Finally, we also found that "knockdown" of the endogenous aPKCζ activity markedly increased basal lipid synthesis and apoptosis, suggesting its constitutive activity in suppressing these processes. Collectively, our findings strongly argue for the fact that certain PKCs have pivotal, isoform-specific, differential, and antagonistic roles in the regulation of human sebaceous gland-derived sebocyte biology.Journal of Investigative Dermatology 04/2012; 132(8):1988-97. · 6.31 Impact Factor -
Article: Activation of transient receptor potential vanilloid-3 inhibits human hair growth.
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ABSTRACT: In the current study, we aimed at identifying the functional role of transient receptor potential vanilloid-3 (TRPV3) ion channel in the regulation of human hair growth. Using human organ-cultured hair follicles (HFs) and cultures of human outer root sheath (ORS) keratinocytes, we provide the first evidence that activation of TRPV3 inhibits human hair growth. TRPV3 immunoreactivity was confined to epithelial compartments of the human HF, mainly to the ORS. In organ culture, TRPV3 activation by plant-derived (e.g., eugenol, 10-1,000 μM) or synthetic (e.g., 2-aminoethoxydiphenyl borate, 1-300 μM) agonists resulted in a dose-dependent inhibition of hair shaft elongation, suppression of proliferation, and induction of apoptosis and premature HF regression (catagen). Human ORS keratinocytes also expressed functional TRPV3, whose stimulation induced membrane currents, elevated intracellular calcium concentration, inhibited proliferation, and induced apoptosis. Of great importance, these effects on ORS keratinocytes were all mediated by TRPV3, as small interfering RNA-mediated silencing of TRPV3 effectively abrogated the cellular actions of the above agonists. These findings collectively support the concept that TRPV3 signaling is a significant player in human hair growth control. Therefore, TRPV3 and the related intracellular signaling mechanism might function as a promising target for pharmacological manipulations of clinically relevant hair growth disorders.Journal of Investigative Dermatology 05/2011; 131(8):1605-14. · 6.31 Impact Factor -
Article: "Sebocytes' makeup": novel mechanisms and concepts in the physiology of the human sebaceous glands.
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ABSTRACT: The pilosebaceous unit of the human skin consists of the hair follicle and the sebaceous gland. Within this "mini-organ", the sebaceous gland has been neglected by the researchers of the field for several decades. Actually, it was labeled as a reminiscence of human development ("a living fossil with a past but no future"), and was thought to solely act as a producer of sebum, a lipid-enriched oily substance which protects our skin (and hence the body) against various insults. However, due to emerging research activities of the past two decades, it has now become evident that the sebaceous gland is not only a "passive" cutaneous "relic" to establish the physico-chemical barrier function of the skin against constant environmental challenges, but it rather functions as an "active" neuro-immuno-endocrine cutaneous organ. This review summarizes recent findings of sebaceous gland research by mainly focusing on newly discovered physiological functions, novel regulatory mechanisms, key events in the pathology of the gland, and future directions in both experimental and clinical dermatology.Pflügers Archiv - European Journal of Physiology 03/2011; 461(6):593-606. · 4.46 Impact Factor -
Article: Endocannabinoids modulate human epidermal keratinocyte proliferation and survival via the sequential engagement of cannabinoid receptor-1 and transient receptor potential vanilloid-1.
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ABSTRACT: We have recently shown that lipid mediators of the emerging endocannabinoid system (ECS) are key players of growth control of the human pilosebaceous unit. In this study, we asked whether the prototypic endocannabinoid anandamide (N-arachidonoylethanolamine, AEA) has a role in growth and survival of epidermal keratinocytes (KCs). Using human cultured KCs and skin organ-culture models, and by employing combined pharmacological and molecular approaches, we provide early evidence that AEA markedly suppresses KC proliferation and induces cell death, both in vitro and in situ. Moreover, we present that these cellular actions are mediated by a most probably constitutively active signaling mechanism that involves the activation of the metabotropic cannabinoid receptor CB(1) and a sequential engagement of the "ionotropic cannabinoid receptor" transient receptor potential vanilloid-1 (TRPV1). Finally, we demonstrate that the cellular effects of AEA are most probably due to a Ca(2+) influx via the non-selective, highly Ca(2+)-permeable ion channel TRPV1, and the concomitant elevation of intracellular Ca(2+) concentration. The data reported here may encourage one to explore whether the targeted manipulation of the above signaling pathway of the cutaneous ECS could become a useful adjunct treatment strategy for hyperproliferative human dermatoses such as psoriasis or KC-derived skin tumors.Journal of Investigative Dermatology 01/2011; 131(5):1095-104. · 6.31 Impact Factor
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Institutions
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2011–2013
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University of Debrecen
- Department of Physiology
Debrecen, Hajdu-Bihar, Hungary
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