Skin homeostasis during inflammation: a role for nerve growth factor.
The skin is a neuroendocrine immune organ in which many different molecules operate in autocrine-paracrine manner to guarantee tissue homeostatsis in physiological and pathophysiological conditions. In this paper we examined NGF and p75 receptor expression in the skin, during CFA induced inflammation, in a time-course study. We also examined cutaneus innervation and proliferation, by means of immunohistochemistry and quantitative image analysis, RT-PCR and Western blot. Spontaneous and evoked pain-behavior was also measured in experimental rats. The main results can be summarized as follows: 1). a peripheral sensory neuropathy develops in this condition, as indicated by thermal hyperalgesia, thus leading to a sensory denervation of the hind-paw skin as indicated by disappearance of CGRP and PGP9.5-IR fibers; 2). NGF and p75 expression (mRNA and protein) increases in the skin (keratinocytes) in the acute phase of CFA inflammation; 3). at this stage, a higher proliferative activity is observed in the skin, as defined by the expression of cell cycle-associated protein Ki67; 4). in the long-lasting chronic phase there is a further up-regulation of NFG and p75 expression in the skin; 5). trkA mRNA expression inversely correlates with p75 and NGF mRNA expression. These results suggest that CFA chronic inflammation evolves from inflammation to a small fibers sensory neuropathy and NGF seems to play a role in both events.
Sivilia
S
S
Department of Veterinary Morphophysiology and Animal Production (DIMORFIPA), University of Bologna, Bologna, Italy.
Paradisi
M
M
D'Intino
G
G
Fernandez
M
M
Pirondi
S
S
Lorenzini
L
L
Calzà
L
L
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D005620:Freund's Adjuvant; D006706:Homeostasis / Q000502:physiology*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism; D012867:Skin / Q000378:metabolism* / Q000473:pathology
D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D005620:Freund's Adjuvant; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D015740:Calcitonin Gene-Related Peptide