Psoriasis : Neuro-Immunologic Cascade And Its Implication In Therapy
In recent time, significant progress has been made to elucidate the pathogenesis of psoriasis: still the molecular basis of the inflammatory and proliferative processes of psoriasis is largely unknown. Role of neurogenic inflammation has provided a new dimension in understanding the pathogenesis of...
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| Main Authors: | , |
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| Format: | Book |
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Wolters Kluwer Medknow Publications,
2003-01-01T00:00:00Z.
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| Summary: | In recent time, significant progress has been made to elucidate the pathogenesis of psoriasis: still the molecular basis of the inflammatory and proliferative processes of psoriasis is largely unknown. Role of neurogenic inflammation has provided a new dimension in understanding the pathogenesis of various cutaneous and systemic inflammatory diseases, such as atopic dermatitis, urticaria, rheumatoid arthritis, ulcerative colitis and bronchial asthma. In this article we have addressed certain key events responsible in the development of a psoriatic lesion. Significant are the proliferation of nerves, upregulation of neuropeptides and increased levels of nerve growth factor (NGF). In immunoperoxidase studies, we found that keratinocytes in lesional and non-lesional psoriatic tissue express high levels of NGF. In the terminal cutaneous nerves of psoriatic lesions, there is a marked upregulation of NGF receptors (NGF-R): p75 neurotrophin receptor (p75NTR) and tyrosine kinase A (TrKA). As keratinocytes of psoriatic plaques express increased levels of NGF, it is likely that murine nerves will promptly proliferate into the transplanted plaques on a severe combined immunodeficient (SCID) mouse. Indeed, we have noted marked proliferation of nerve fibers in transplanted normal human skin. These observations, as well as recent findings about NGF â€"induced chemokine expression in keratinocytes, further substantiate a contributing role of NGE and its receptor system (p75 NTR /TrkA) in the pathogenesis of psoriasis. A new discipline has emerged in clinical pharmacology focusing on development of drugs targeting the neuropetides (NP), NP receptors and the NGF/NGF-R system. Currently, we are evaluating antagonists to selected neuropeptides and NGF/NGF-R, with the expectation of identifying pharmacological agents to counter neurogentic inflammation in psoriasis. |
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| Item Description: | 0019-5154 1998-3611 |