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Abstract: The aims of this study were to examine content and expression level of proopiomelanocortin (POMC) mRNA variants in human dermal fibroblasts (HDF) as compared to primary keratinocytes and HaCaT cells of keratinocyte origin. Primary fibroblasts and keratinocytes were obtained from normal human foreskin. Full-length and total (i.e. the full-length, truncated and/or alternatively spliced) POMC mRNA in skin cells were determined by qRT-PCR using specific probes. The full-length POMC mRNA in HDF is neither constitutively expressed, nor could be induced by corticotropin releasing hormone (CRH) or cytokines interferon γ (IFN-γ) and transforming growth factor-β1 (TGF-β1). However, the truncated/alternatively spliced POMC mRNA variants are constitutively expressed in HDF and could be moderately increased with CRH and the cytokines. Primary keratinocytes, in addition to truncated/alternatively spliced POMC mRNA variants, also constitutively express full-length POMC mRNA, both being downregulated during in vitro culturing. Unlike primary keratinocytes, HaCaT cells, express only truncated/alternatively spliced POMC mRNA variants. The level of POMC mRNA expression in HaCaT cells was associated with differentiation stage, being higher in more differentiated cells. Thus, in this study we have shown for the first time that HDF do not express the full-length POMC mRNA, either constitutively or upon activation, opposing to primary keratinocytes which constitutively express the full-length POMC mRNA as a minor variant. Although expressing only truncated/alternatively spliced POMC mRNA variant, HDF express POMC peptide, showing that those transcriptional variants are translatable. Truncated/alternatively spliced POMC mRNA variants, expressed both in HDF and keratinocytes are subjected to regulation, implicating their functionality. Furthermore, the IFN-γ-induced up-regulation at transcriptional level was associated with increased level of POMC peptide detected in HDF lysates. Thus, data of this study have shown that HDF express only truncated/alternatively spliced POMC mRNA variants, which are probably biologically relevant as they could be translated to POMC peptide, both constitutively and upon activation. [Copyright &y& Elsevier]

Summary: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) represents the most common form of prostatitis. No known etiology factor in most cases can be found. It is possible that at least in some cases autoimmune response could be causative factor. Common treatment options include antibiotics, alpha blockers, myorelaxants, phytotherapeuticals, non steroidal anti-inflammatory drugs, hormonal treatment and surgery but corticosteroids have not been investigated. Hypothesis: Chronic pelvic pain syndrome is in some cases autoimmune disease and this could have repercussions on treatment using low dose corticosteroids. Rationale: Currently corticosteroids are not a standard treatment option in CP/CPPS. Theoretical, experimental and scarce clinical evidence suggest that treatment with low dose corticosteroids could be beneficial in some patients with chronic prostatitis. If our hypothesis could be supported with well designed, randomized clinical trials this could change the approach of the medical treatment of CP/CPPS. [Copyright &y& Elsevier]