Proceedings of the National Academy of Sciences - PNAS, 2009-08, Vol.106 (31), p.13088-13093
2009
Details
- Autor(en) / Beteiligte
- Titel
- Impaired defense mechanism against inflammation, hyperalgesia, and airway hyperreactivity in somatostatin 4 receptor gene-deleted mice
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2009-08, Vol.106 (31), p.13088-13093
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2009
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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 sst₄ 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.0900681106Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2722291
- Format
- –
- Schlagworte
- Airway management, Analgesics, Animals, Antiinflammatories, Arthritis, Biological Sciences, Bronchial Hyperreactivity - etiology, Bronchial Hyperreactivity - prevention & control, Cytokines, Dermatitis, Allergic Contact - etiology, Edema, Female, Hyperalgesia, Hyperalgesia - etiology, Hyperalgesia - prevention & control, Inflammation, Inflammation - etiology, Inflammation - prevention & control, Lipopolysaccharides - toxicity, Lung diseases, Lungs, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Oxazolone - toxicity, Receptors, Receptors, Somatostatin - deficiency, Receptors, Somatostatin - genetics, Receptors, Somatostatin - physiology, Rodents, Somatostatin receptors, T cell receptors