Corticotropin-releasing hormone stimulates NF-kappaB in human epidermal keratinocytes

Zbytek, Blazej; Pfeffer, Lawrence M.; Słomiński, Andrzej

doi:10.1677/joe.0.181r001

Cited by 60 publications

(59 citation statements)

References 37 publications

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“…UV radiation and factors raising intracellular cAMP increase CRH-R1α expression and change the pattern of isoform expression Slominski et al, 2001). CRH-R1 participates in the regulation of skin cell proliferation, apoptosis, differentiation and immune activities (Carlson et al, 2001;Quevedo et al, 2001;Slominski, 2005;Slominski et al, 2000d;Slominski et al, 2006b;Zbytek et al, 2004;Zbytek and Slominski, 2005).…”

Section: Cutaneous Crh Signaling Systemmentioning

confidence: 99%

“…Mediators of this axis, i.e., CRH, urocortin and POMC peptides, would then regulate skin pigmentary, immune, epidermal, dermal and adnexal systems Ito et al, 2005;Kauser et al, 2006;Slominski, 2005;Slominski et al, 2004b;Slominski and Wortsman, 2000;Slominski et al, 1999c;Zbytek et al, 2004;Zouboulis et al, 2002). Accordingly, exposure to, for example, UV light (physical stress), or biological or chemical stress, would activate pathways involved in the local production of CRH and CRH related peptides and POMC-derived peptides (Slominski et al, 1996b;Slominski et al, 2004b;Slominski and Wortsman, 2000;Slominski et al, 1999c;Zbytek et al, 2006).…”

Section: Functionality Of the Cutaneous Hpa Axis Homologmentioning

confidence: 99%

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Differential expression of HPA axis homolog in the skin

Slominski

Wortsman

Tuckey

et al. 2007

Molecular and Cellular Endocrinology

253

267

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SummaryHuman skin expresses elements of the hypothalamo-pituitary-adrenal (HPA) axis including proopiomelanocortin (POMC), corticotropin releasing hormone (CRH), the CRH receptor-1 (CRH-R1), key enzymes of corticosteroid synthesis and synthesizes glucocorticoids. Expression of these elements is organized in functional, cell type-specific regulatory loops, which imitate the signaling structural hierarchy of the HPA axis. In melanocytes and fibroblasts CRH-induced CRH-R1 stimulation upregulates POMC expression and production of ACTH through activation of cAMP dependent pathway(s). Melanocytes respond with enhanced production of cortisol and corticosterone, which is dependent on POMC activity. Fibroblasts respond to CRH and ACTH with enhanced production of corticosterone, but not cortisol, which is produced constitutively. Organcultured human scalp hair follicles also show a fully functional HPA axis equivalent, including cortisol synthesis and secretion and negative feedback regulation by cortisol on CRH expression. Thus differential, CRH-driven responses of skin reproduce key features of the central HPA axis at the tissue/single cell levels.

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Section: Cutaneous Crh Signaling Systemmentioning

confidence: 99%

Section: Functionality Of the Cutaneous Hpa Axis Homologmentioning

confidence: 99%

Differential expression of HPA axis homolog in the skin

Slominski

Wortsman

Tuckey

et al. 2007

Molecular and Cellular Endocrinology

253

267

View full text Add to dashboard Cite

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“…In other cell types, such as keratinocytes, CRH did not stimulate POMC [32]. CRH acted there directly stimulating rather than inhibiting inflammatory response [45].…”

Section: Effect Of Crh On Nf-κb Activity Is Diminished In the Presencmentioning

confidence: 82%

“…This is in contrast to normal epidermal keratinocytes where CRH acts as a proinflammatory agent via activation of CRH-R1 [45]. Thus, the same molecule (CRH) acting on the same receptor (CRH-R1) can induce opposite effects (anti-versus pro-inflammatory) in the same tissue (epidermis) in a cell type specific fashion through overlapping but distinct mechanisms.…”

Section: Concluding Remarkmentioning

confidence: 94%

“…pNF-κB-Luc and pP1-Luc (control without κB sites, empty vector) plasmids were constructed as described previously [30,45]. At 24 h after transfection, the cells cultures were incubated in serum-free medium with or without CRH for 24 h. Then, cells were lysed and luciferase and Renilla luciferase signals were recorded after sequential addition of Luciferase Assay Reagent II and Stop-Glo Reagent (Promega, Madison, WI) using TD-20/20 luminometer (Turner Designs, Sunnyvale, CA).…”

Section: Nf-κb Assaysmentioning

confidence: 99%

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CRH inhibits NF-κB signaling in human melanocytes

2006

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Corticotropin releasing hormone (CRH), a messenger of stress at the central level, is expressed in the epidermis where it operates within local equivalent of hypothalamo-pituitary axis. CRH inhibits NF-κB activity in human immortalized epidermal (PIG1) melanocytes. In melanocytes CRH stimulates pro-opiomelanocortin (POMC) mRNA and adrenocorticotropin (ACTH) peptide production. Knockdown of POMC levels by transfecting cells with antisense oligonucleotides blocks the effect of CRH on NF-κB signaling indicating that the above inhibition is indirect, e.g. through activation of POMC. We suggest that induction of POMC by CRH serves as a feedback mechanism to self-restrict inflammatory response in the skin.

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Aberrant promoter methylation of multiple genes in malignant ovarian tumors and in ovarian tumors with low malignant potential

Wiley

Katsaros

Chen

et al. 2006

Cancer

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BACKGROUND.Methylation‐mediated suppression of detoxification, DNA repair, and tumor suppressor genes has been implicated in cancer development and progression. Studies also have indicated that concordant methylation of multiple genes (methylator phenotypes), rather than a single gene, may predict cancer prognosis. The current study was designed to determine whether a methylator phenotype exists in ovarian cancer, whether methylation frequencies differ between malignant ovarian tumors and ovarian tumors with low malignant potential (LMP or borderline), and whether methylation of multiple genes affects patient survival.METHODS.The current study included 234 consecutively diagnosed patients with either LMP (n = 19 patients) or malignant (n = 215 patients) ovarian tumors. DNA samples were extracted from fresh frozen tissues and were analyzed for methylation in the promoter region of 6 genes (p16, breast cancer 1 [BRCA1], insulin‐like growth factor‐binding protein 3 [IGFBP‐3], glutathione S‐transferase π 1 [GSTP1], estrogen receptor‐α [ER‐α], and human MutL homologue 1 [hMLH1]) by using methylation‐specific polymerase chain reaction analysis.RESULTS.The frequencies of methylation in malignant tumors and LMP tumors were 0% and 0% for GSTP1, respectively; 9% and 0% for hMLH1, respectively; 21% and 5% for BRCA1, respectively; 42% and 21% for p16, respectively; 44% and 26% for IGFBP‐3, respectively; and 57% and 42% for ER‐α, respectively. A methylator phenotype was not detected, but a calculated methylation index (MI) that was based on the total number of genes methylated in each tumor was associated with ovarian cancer risk and progression. A higher MI was associated with malignant tumors (odds ratio, 10.11; 95% confidence interval [95% CI], 1.19–85.75) and disease progression (hazards ratio, 6.53; 95% CI, 1.39–30.65).CONCLUSIONS.Although a methylator phenotype was not identified, the current results suggested that methylation of multiple genes may play an important role in ovarian cancer development and progression and may have clinical implications in prognosis. Cancer 2006. © 2006 American Cancer Society.

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Corticotropin-releasing hormone stimulates NF-kappaB in human epidermal keratinocytes

Cited by 60 publications

References 37 publications

Differential expression of HPA axis homolog in the skin

Differential expression of HPA axis homolog in the skin

CRH inhibits NF-κB signaling in human melanocytes

Aberrant promoter methylation of multiple genes in malignant ovarian tumors and in ovarian tumors with low malignant potential

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