Targeted Disruption of the Galanin Gene Attenuates Inflammatory Responses in Murine Skin

Abstract

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.

Physiology, Signaling, and Pharmacology of Galanin Peptides and Receptors: Three Decades of Emerging Diversity

“…After galanin administration, MPO activity and the acinar cell necrosis score returned to normal levels in the galanin-KO mice, (Bhandari et al, 2010b). However, the reduction in neutrophil accumulation, reflected by reduced MPO activity, in galanin-KO mice is not exclusively restricted to AP and seems to be a more general phenomenon of inflammation, because it has also been observed with inflammatory skin responses (Schmidhuber et al, 2008).…”

“…Galanin-OE mice displayed a significant reduction in cutaneous plasma extravasation induced by mustard oil (Holmberg et al, 2005a). In addition, galanin-KO mice exhibited a deficit in neutrophil accumulation in skin after exposure to noxious heat, carrageenan, or TNF-a (Schmidhuber et al, 2008).…”

Galanin receptor 3 - a potential target for acute pancreatitis therapy

“…Recently, Schmidhuber et al. 32 described an important role for galanin in neurogenic inflammation in the murine skin. Our data suggest a similar phenomenon may occur in the pancreas, indicative of a possible role for galanin in neurogenic inflammation, however, further studies are required to establish this 8,33 …”

Evidence that the Modulatory Effect of Galanin on Inflammatory Edema Formation is Mediated by the Galanin Receptor 3 in the Murine Microvasculature

“…We also demonstrated that the related peptides galanin-like peptide (GALP) and alarin inhibited inflammatory edema formation mediated by substance P and calcitonin gene-related peptide (CGRP) in murine dorsal skin Santic et al 2007). Furthermore, we have examined cutaneous inflammatory responses in galanin knockout mice; however, it was not possible to fully elucidate the role of galanin in the cutaneous microvasculature, as these mice exhibit a developmental deficit that could be responsible for the lack of neurogenic inflammation observed (Schmidhuber et al 2008). …”