Effects of Topical Intranasal Doxycycline Treatment in the Rat Allergic Rhinitis Model
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Objectives. Allergic rhinitis (AR) is a chronic upper respiratory tract disease that inflames the mucous membranes of the nose and occurs when circulating inflammatory cells including eosinophils and basophils migrate to and accumulate in the inflammation area by passing through the interstitium and capillary walls. To pass through these barriers, the in- flammatory cells degrade extracellular matrix proteins. Matrix metalloproteinases (MMPs) released by inflammatory cells mediate the degradation of these proteins. MMPs have synthetic inhibitors and doxycycline, a tetracycline anti- biotic, inhibits MMPs. This study investigated the efficiency of intranasal doxycycline in decreasing the symptoms and inflammatory cell infiltration in an animal model of AR. Methods. AR was created in female Wistar rats by repeated intranasal challenge with ovalbumin by intraperitoneal injection. For 15 days, topical intranasal doxycycline was administered one hour before ovalbumin administration. Following intranasal administration, nasal symptoms were scored and the nasal mucosae of all rats were evaluated histopatho- logically. To investigate tissue changes, hematoxyline-eosin and Alcian blue/periodic acid Schiff stains were used. As well, cilia loss, goblet cell changes, vascular congestion, vascular proliferation, inflammatory cell infiltration, eosinophil infiltration and the degree of hypertrophy in chondrocytes were evaluated with light microscopy. Results. Typical symptoms of AR were decreased by intranasal doxycycline administration. These effects were stable after repeated intranasal ovalbumin administration. Histological evaluation of doxycycline treated rats did not reveal typi- cal inflammatory changes associated with AR. Conclusion. MMPs may have crucial functions in AR and topical intranasal doxycycline, which decreases inflammatory cell infiltration, may offer an alternative therapy for AR.
Abstract
Objectives. Allergic rhinitis (AR) is a chronic upper respiratory tract disease that inflames the mucous membranes of the nose and occurs when circulating inflammatory cells including eosinophils and basophils migrate to and accumulate in the inflammation area by passing through the interstitium and capillary walls. To pass through these barriers, the in- flammatory cells degrade extracellular matrix proteins. Matrix metalloproteinases (MMPs) released by inflammatory cells mediate the degradation of these proteins. MMPs have synthetic inhibitors and doxycycline, a tetracycline anti- biotic, inhibits MMPs. This study investigated the efficiency of intranasal doxycycline in decreasing the symptoms and inflammatory cell infiltration in an animal model of AR. Methods. AR was created in female Wistar rats by repeated intranasal challenge with ovalbumin by intraperitoneal injection. For 15 days, topical intranasal doxycycline was administered one hour before ovalbumin administration. Following intranasal administration, nasal symptoms were scored and the nasal mucosae of all rats were evaluated histopatho- logically. To investigate tissue changes, hematoxyline-eosin and Alcian blue/periodic acid Schiff stains were used. As well, cilia loss, goblet cell changes, vascular congestion, vascular proliferation, inflammatory cell infiltration, eosinophil infiltration and the degree of hypertrophy in chondrocytes were evaluated with light microscopy. Results. Typical symptoms of AR were decreased by intranasal doxycycline administration. These effects were stable after repeated intranasal ovalbumin administration. Histological evaluation of doxycycline treated rats did not reveal typi- cal inflammatory changes associated with AR. Conclusion. MMPs may have crucial functions in AR and topical intranasal doxycycline, which decreases inflammatory cell infiltration, may offer an alternative therapy for AR.
참고문헌 (17)
- Golub LM, "Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mechanisms", Adv Dent Res, 12(2), pp.12~26 (1998)
- Asano K, "Suppressive activity of fexofenadine hydrochloride on metalloproteinase production from nasal fibroblasts in vitro", Clin Exp Allergy, 34(12), pp.1890~1898 (2004)
- De S, "Matrix metalloproteinases and their inhibitors innon-neoplastic otorhinolaryngological disease", J Laryngol Otol, 119(6), pp.436~442 (2005)
- Lee KS, "Matrix metalloproteinase inhibitor regulatesinflammatory cell migration by reducing ICAM-1 and VCAM-1 expression in a murine model of toluene diisocyanate-induced asthma", J Allergy Clin Immunol, 111(6), pp.1278~1284 (2003)
- Baltacıoglu E, "Tetracyclines and their non-antimicrobial properties: a new approach to their use in periodontal treatment", Hacettepe Dişhekimliği Fakültesi Dergisi, 30(1), pp.97~107 (2006)
- Wen WD, "Botulinum toxin therapy in the ovalbumin-sensitized rat", Neuroimmunomodulation, 14(2), pp.78~83 (2007)
- Salib RJ, "Remodelling of the upper airways in allergic rhinitis: is it a feature of the disease?", Clin Exp Allergy, 33(12), pp.1629~1633 (2003)
- Bousquet J, "Allergic rhinitis: a disease remodeling the upper airways?", J Allergy Clin Immunol, 113(1), pp.43~49 (2004)
- Ercan I, "Effects oftopical application of methotrexate on nasal mucosa in rats: a preclinicalassessment study", Otolaryngol Head Neck Surg, 134(5), pp.751~755 (2006)
- Shimizu S, "Th2 cytokine inhibitor suplatasttosilate inhibits antigen-induced mucus hypersecretion in the nasal epithelium of sensitized rats", Ann Otol Rhinol Laryngol, 118(1), pp.67~72 (2009)
- Bentley AM, "Immunohistology of the nasal mucosa in seasonalallergic rhinitis: increases in activated eosinophils and epithelial mast cells", J Allergy Clin Immunol, 89(4), pp.877~883 (1992)
- Herouy Y, "Inflammation in stasis dermatitis upregulates MMP-1, MMP-2 and MMP-13 expression", J Dermatol Sci, 25(3), pp.198~205 (2001)
- Ohno I, "Eosinophils as a source of matrix metalloproteinase-9 in asthmatic airway inflammation", Am J Respir Cell Mol Biol, 16(3), pp.212~219 (1997)
- Okada S, "Migration of eosinophils through basement membrane components in vitro: role of matrix metalloproteinase-9", Am J Respir Cell Mol Biol, 17(4), pp.519~528 (1997)
- Nakaya M, "Prolonged allergen challenge in murine nasal allergic rhinitis: nasal airway remodeling and adaptation of nasal airway responsiveness", Laryngoscope, 117(5), pp.881~885 (2007)
- Namba M, "Suppression of matrix metalloproteinase production from nasal fi broblasts by fluticasone propionate in vitro", Acta Otolaryngol, 124(8), pp.964~969 (2004)
- Sakakura Y, "Absorption of various drugs through the rabbit’s respiratory mucosa in vitro", Arch Otorhinolaryngol, 238(1), pp.87~96 (1983)