RESUMO
The inflammatory response after skin injury involves the secretion of a variety of cytokines and growth factors that are necessary for tissue repair. Caspase recruitment domain-containing protein 9 (CARD9) is an essential signalling adaptor molecule for NF-κB activation upon triggering through C-type lectin receptors (CLRs), which are expressed in macrophages and dendritic cells. However, the role of CARD9 in inflammatory responses at the wound site has not been elucidated. In this study, we analysed the role of CARD9 in the healing process of skin wounds. Wounds were created on the backs of wild-type (WT) C57BL/6 mice and CARD9 gene-disrupted (knockout [KO]) mice. We analysed per cent wound closure, and the wound tissues were harvested for analysis of leucocyte accumulation and cytokine and chemokine expressions. CARD9KO mice exhibited significant attenuation of wound closure compared with WT mice on days 5, 7 and 10 postwounding, which was associated with decreased macrophage accumulation and reduced TNF-α, IL-1ß, CCL3 and CCL4 expressions. These results suggest that CARD9 may be involved in the wound-healing process through the regulation of macrophage-mediated inflammatory responses.
Assuntos
Proteínas Adaptadoras de Sinalização CARD/metabolismo , Macrófagos , Transdução de Sinais , Pele/metabolismo , Pele/patologia , Cicatrização , Animais , Proteínas Adaptadoras de Sinalização CARD/genética , Quimiocina CCL3/genética , Quimiocina CCL3/metabolismo , Feminino , Expressão Gênica , Inflamação/patologia , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Contagem de Leucócitos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , RNA Mensageiro/metabolismo , Pele/lesões , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Cicatrização/efeitos dos fármacos , Zimosan/farmacologiaRESUMO
The stomatitis caused by anticancer agents and radiation therapy deteriorates patient QOL, potentially causing eating disorders as a result of pain. Although gargling and ointments can be used in the treatment of stomatitis, patients must spit out mouthwash after use, while ointment application requires a finger to be inserted into the oral cavity. In contrast, sprays eliminate these potential compliance problems. Therefore, we developed a stomatitis spray that remains on the oral mucosa. It has been reported that irsogladine maleate (IM) is effective against stomatitis via oral administration. IM is water insoluble; thus, it was dissolved with various cyclodextrins (CDs). Furthermore, we examined combination with gum ghatti (GG), a mucoadhesive polymer. The interaction between mucin and GG was examined by Quartz Crystal Microbalance with Dissipation monitoring. We found that GG exhibited mucoadhesion. Furthermore, we examined the healing effects of IM on stomatitis in a stomatitis model hamster. We found that stomatitis healed after direct application of IM. However, the model used in this experiment is not based on stomatitis caused by anticancer agents. Further study is therefore necessary.