Targeted disruption of the galanin gene attenuates inflammatory responses in murine skin.
The release of neuropeptides from primary sensory nerve fibers has been implicated in the modulation of local immune responses in surface tissues, such as the skin and the gastrointestinal mucosa, thereby inducing neurogenic inflammation, which is characterized by plasma extravasation and vasodilatation. In addition, cytokines, either alone or in conjunction with neuropeptides, initiate recruitment of immunocompetent cells such as neutrophils during the initial phases of inflammation. Growing evidence suggests that the neuropeptide galanin plays an important role in skin immune defense and pathophysiology. In this paper, we report that adult mice carrying a loss-of-function mutation in the galanin gene (galanin knockout, Gal KO) demonstrate an absence of the normal neurogenic inflammatory response, upon treatment of the skin either with the vanilloid receptor 1 agonist capsaicin or noxious heat. Furthermore, a lack of an acute inflammatory edema induced by coinjection of substance P and calcitonin gene-related peptide was observed. In addition, Gal KO animals also exhibit a deficit in neutrophil accumulation in the skin after exposure to noxious heat, carrageenin, or tumor necrosis factor alpha. These data indicate that Gal KO mice demonstrate abnormal neurogenic inflammatory responses in murine skin compared to strain-matched wild-type mice.
Schmidhuber
Sabine M
SM
Department of Pediatrics, University Hospital Salzburg, Paracelsus Medical University Salzburg, Muellner-Hauptstrasse 48, 5020 Salzburg, Austria.
Starr
Anna
A
Wynick
David
D
Kofler
Barbara
B
Brain
Susan D
SD
D000818:Animals; D000982:Antipruritics / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D002351:Carrageenan / Q000378:metabolism; D019004:Galanin / Q000235:genetics / Q000378:metabolism; D018390:Gene Targeting; D006358:Hot Temperature; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018377:Neurotransmitter Agents / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013373:Substance P / Q000378:metabolism
D000982:Antipruritics; D018377:Neurotransmitter Agents; D013373:Substance P; D019004:Galanin; D002351:Carrageenan; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin