Impaired defense mechanism against inflammation, hyperalgesia, and airway hyperreactivity in somatostatin 4 receptor gene-deleted mice

Z. Helyes, E. Pintér, K. Sándor, K. Elekes, Ágnes Bánvölgyi, Dániel Keszthelyi, E. Szöke, Dániel M. Tóth, Zoltán Sándor, L. Kereskai, G. Pozsgai, Jeremy P. Allen, Piers C. Emson, Adrienn Markovics, J. Szolcsányi

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

We have shown that somatostatin released from activated capsaicin-sensitive nociceptive nerve endings during inflammatory processes elicits systemic anti-inflammatory and analgesic effects. With the help of somatostatin receptor subtype 4 gene-deleted mice (sst4 -/-), we provide here several lines of evidence that this receptor has a protective role in a variety of inflammatory disease models; several symptoms are more severe in the sst 4 knockout animals than in their wild-type counterparts. Acute carrageenan-induced paw edema and mechanical hyperalgesia, inflammatory pain in the early phase of adjuvant-evoked chronic arthritis, and oxazolone-induced delayed-type hypersensitivity reaction in the skin are much greater in mice lacking the sst4 receptor. Airway inflammation and consequent bronchial hyperreactivity elicited by intranasal lipopolysaccharide administration are also markedly enhanced in sst4 knockouts, including increased perivascular/peribronchial edema, neutrophil/macrophage infiltration, mucus-producing goblet cell hyperplasia, myeloperoxidase activity, and IL-1β, TNF-α, and IFN-γ expression in the inflamed lung. It is concluded that during these inflammatory conditions the released somatostatin has pronounced counterregulatory effects through sst4 receptor activation. Thus, this receptor is a promising novel target for developing anti-inflammatory, analgesic, and anti-asthmatic drugs.

Original languageEnglish
Pages (from-to)13088-13093
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number31
DOIs
Publication statusPublished - Aug 4 2009

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Hyperalgesia
Defense Mechanisms
Non-Steroidal Anti-Inflammatory Agents
Inflammation
Somatostatin
Edema
Oxazolone
Anti-Asthmatic Agents
Genes
Bronchial Hyperreactivity
Intranasal Administration
Goblet Cells
Nerve Endings
Neutrophil Infiltration
Carrageenan
Capsaicin
Delayed Hypersensitivity
Mucus
Interleukin-1
Peroxidase

Keywords

  • Allergic contact dermatitis
  • Arthritis
  • Capsaicin-sensitive afferents
  • Endotoxin-induced pneumonitis
  • Inflammatory cytokines

ASJC Scopus subject areas

  • General

Cite this

Impaired defense mechanism against inflammation, hyperalgesia, and airway hyperreactivity in somatostatin 4 receptor gene-deleted mice. / Helyes, Z.; Pintér, E.; Sándor, K.; Elekes, K.; Bánvölgyi, Ágnes; Keszthelyi, Dániel; Szöke, E.; Tóth, Dániel M.; Sándor, Zoltán; Kereskai, L.; Pozsgai, G.; Allen, Jeremy P.; Emson, Piers C.; Markovics, Adrienn; Szolcsányi, J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 31, 04.08.2009, p. 13088-13093.

Research output: Contribution to journalArticle

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AU - Sándor, K.

AU - Elekes, K.

AU - Bánvölgyi, Ágnes

AU - Keszthelyi, Dániel

AU - Szöke, E.

AU - Tóth, Dániel M.

AU - Sándor, Zoltán

AU - Kereskai, L.

AU - Pozsgai, G.

AU - Allen, Jeremy P.

AU - Emson, Piers C.

AU - Markovics, Adrienn

AU - Szolcsányi, J.

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