CRF and Related Peptides as Anti‐Inflammatory Agonistsa

Thomas, Holly A.; Ling, N; Wei, E.T.

doi:10.1111/j.1749-6632.1993.tb49934.x

Cited by 19 publications

(8 citation statements)

References 23 publications

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“…Local CRH injection into the hindpaw also inhibits inflammatory oedema formation (45). This is supported by several studies demonstrating that CRH administered into the periphery exerts anti‐inflammatory effects (46).…”

Section: Peripheral Crh As An Immunomodulatory Mediatormentioning

confidence: 58%

The role of corticotropin‐releasing hormone in immune‐mediated cutaneous inflammatory disease

O'Kane

Murphy

Kirby

2006

Experimental Dermatology

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Corticotropin-releasing hormone (CRH) coordinates the systemic stress response via hypothalamic-pituitary-adrenal (HPA) axis activation with subsequent modulation of the inflammatory response. Stress is known to affect expression of immune-mediated inflammatory diseases, many of which are associated with HPA axis abnormalities. HPA axis components including CRH and its receptors (CRH-R) exist in the skin and exhibit differential expression according to cell type, physiological fluctuations and disease states. This confirms a local functioning cutaneous HPA-like system. Peripheral CRH may exhibit proinflammatory effects. Animal studies confirm that peripheral CRH is required for induction of the inflammatory response in vivo. CRH and CRH-R are upregulated in inflammatory arthritis synovium and psoriatic skin. CRH may influence mast cell activation, direct modulation of immune cells, angiogenesis and induction of the novel orphan nuclear receptor NURR1. This transcription factor is part of the steroid/thyroid superfamily of related nuclear receptors that includes receptors for steroids, retinoids and vitamin D; ligands of these receptors are effective in treating psoriasis. The roles of CRH and NURR1 in psoriasis and inflammatory skin diseases, especially those associated with stress, remain to be elucidated. This stress may be psychological or physical. CRH, produced locally or delivered by peripheral nerves, may mediate interactions between a cutaneous HPA axis-like system and the central HPA axis--the "brain-skin axis".

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Section: Peripheral Crh As An Immunomodulatory Mediatormentioning

confidence: 58%

The role of corticotropin‐releasing hormone in immune‐mediated cutaneous inflammatory disease

O'Kane

Murphy

Kirby

2006

Experimental Dermatology

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“…The most proximal component of both the central and peripheral HPA axis is CRH, which is expressed in combination with its receptors (CRH‐Rs) in human skin and on many immune cells, where it may have either pro‐ or anti‐inflammatory effects . There are conflicting reports on the expression of CRH and CRH‐R in psoriasis.…”

Section: Proposed Pathophysiology Of the Stress–psoriasis Associationmentioning

confidence: 99%

“…The most proximal component of both the central and peripheral HPA axis is CRH, which is expressed in combination with its receptors (CRH-Rs) in human skin 38 and on many immune cells, 39,40 where it may have either pro-or anti-inflammatory effects. [41][42][43][44] There are conflicting reports on the expression of CRH and CRH-R in psoriasis. Tagen et al 45 found reduced expression of CRH-R1 in affected skin and elevated serum CRH levels in patients compared with controls, while Zhou et al 46 found reduced CRH and CRH-R1 expression in involved skin compared with uninvolved and control skin.…”

Section: Hypothalamic-pituitary-adrenal Axis and Sympatheticadrenal-mmentioning

confidence: 99%

Does psychosocial stress play a role in the exacerbation of psoriasis?

2013

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It is widely accepted that psychosocial stress can result from the daily strains of living with a diagnosis of psoriasis. There is now an evolving body of work to suggest that psychosocial stress may also play a role in the exacerbation of psoriasis. We discuss the historical evidence supporting a temporal relationship between psychosocial stress and the exacerbation of psoriasis. The underlying pathophysiological mechanisms by which this occurs are largely unknown, but current evidence points towards a role for nerve-related factors, namely their interaction with mast cells and the potentiation of neurogenic inflammation in this regard. It is also likely that the physiological stress response in patients with psoriasis differs from that in healthy individuals, as evidenced by alterations in the hypothalamic-pituitary-adrenal axis and sympathetic-adrenal-medullary system function. Psychological stress results in a redistribution of leucocytes with increased trafficking of inflammatory cells into the skin, which may exacerbate psoriasis. Langerhans cells play a role in the stress response of normal skin; their function in the stress response of patients with psoriasis is open to speculation. We discuss the influence of stress reactivity in patients with psoriasis and the impact of stress reduction strategies in the management of psoriasis. Finally, we suggest potentially fruitful areas for future research.

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“…Several groups have noted heterogeneous forms of CRH‐ir in human immune tissues (3, 5, 15, 28) but little effort has been made to characterize these variant forms. In addition to reports that peripheral CRH can exert pro‐inflammatory actions, there is also evidence for anti‐inflammatory effects of CRH (33). These apparently conflicting reports may reflect differential degradation of CRH under different experimental conditions into fragments with their own selective activity.…”

Section: Discussionmentioning

confidence: 99%

Corticotropin‐Releasing Hormone Immunoreactivity in Human T and B Cells and Macrophages: Colocalization With Arginine Vasopressin

Baker

Richards

Dayan

et al. 2003

J Neuroendocrinology

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Corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) are expressed in cells of the immune system where they exert immunomodulatory roles, but these neuropeptides are poorly characterized in human immune tissues. The aim of this study was to determine concentrations and distribution of CRH and AVP in nonactivated human peripheral blood mononuclear cells (PBMC). PBMC from normal human subjects were separated into enriched subpopulations of T and B cells and monocytes/macrophages by a magnetic bead/monoclonal antibody technique. CRH and AVP were measured in cell extracts by radioimmunoassay (RIA). CRH-immunoreactivity (ir) ranged 0.24-0.8 fmol/million cells (n = 6 subjects) in T cell extracts, 0.4-2.7 fmol/million cells (n = 4) in B cells and 0.63-2.16 fmol/million cells (n = 4) in macrophages. AVP-ir ranged 0.2-0.95 fmol/million cells in T cell extracts, <0.1-0.8 fmol/million cells in B cells and 0.14-3.19 fmol/million cells in macrophages. Reversed-phase high-performance liquid chromatography (HPLC) of T and B cell extracts revealed a peak of CRH-ir which coeluted with synthetic CRH-41; this peak was not present in macrophages. A second peak of CRH-ir which eluted in a more hydrophobic position was observed in extracts of T and B cells and macrophages. This unidentified form of CRH-ir is the predominant form of CRH-ir in nonactivated human PBMC. This is the first study to demonstrate that CRH-ir and AVP-ir are colocalized within human T cells, B cells and monocytes/macrophages. We have confirmed observations of a variant form of CRH-ir in human PBMC and show that this is the predominant form in macrophages and B cells whereas CRH-ir, which coelutes with CRH(1-41) on HPLC, is present in significant amounts only in T cells. These data also confirm that CRH-ir in human PBMC is not urocortin because the antiserum used in the CRH RIA does not bind to urocortin.

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CRF and Related Peptides as Anti‐Inflammatory Agonistsa

Cited by 19 publications

References 23 publications

The role of corticotropin‐releasing hormone in immune‐mediated cutaneous inflammatory disease

The role of corticotropin‐releasing hormone in immune‐mediated cutaneous inflammatory disease

Does psychosocial stress play a role in the exacerbation of psoriasis?

Corticotropin‐Releasing Hormone Immunoreactivity in Human T and B Cells and Macrophages: Colocalization With Arginine Vasopressin

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