Toll-like receptor 2 activation induces C-C motif chemokine ligand 5 production in canine keratinocytesTakahashi, Kaho; Yoshimatsu, Rina; Kaida, Yuzuki; Hasegawa, Takehiro; Ohmori, Keitaro
VETERINARY DERMATOLOGY
WILEY
BackgroundToll-like receptor 2 (TLR2) in keratinocytes can be activated by Staphylococcus spp. that are frequently detected on the skin of dogs with atopic dermatitis (AD). C-C motif chemokine ligand 5 (CCL5) produced by keratinocytes has been considered to be involved in the pathogenesis of canine AD (cAD). However, whether TLR2 activation induces CCL5 production in canine keratinocytes remains unclear.Hypothesis/ObjectivesTo elucidate the effect of TLR2 agonists on CCL5 production in canine keratinocytes, possible synergy with interferon (IFN)-gamma, interleukin (IL)-13 or IL-4 and underlying mechanisms.Materials and MethodsCanine progenitor epidermal keratinocyte (CPEK) cells were stimulated with TLR2 agonists with or without inhibitors of the TLR2 signalling pathway or IFN-gamma, a T-helper (Th)1-type cytokine and/or IL-13 or IL-4, a Th2-type cytokine. CCL5 protein concentrations in the culture supernatant were measured by enzyme-linked immunosorbent assay. Additionally, TLR2 mRNA expression was measured by real-time PCR in CPEK cells stimulated with IFN-gamma.ResultsTLR2 agonists increased CCL5 production in CPEK cells. Inhibitors of the TLR2 signalling pathway suppressed CCL5 production. IFN-gamma, but not IL-13 or IL-4, synergistically enhanced TLR2 agonist-induced CCL5 production. IFN-gamma partially increased TLR2 mRNA expression in CPEK cells.Conclusions and Clinical RelevanceTLR2 activation by Staphylococcus spp. may produce CCL5 in canine keratinocytes, thereby recruiting immune cells into the skin of dogs with AD. During the Th1-activated chronic phase of cAD, where TLR2 expression may be partially upregulated, Staphylococcus spp. may exacerbate skin inflammation. Further studies are warranted to determine the clinical significance and mechanisms of skin bacteria-mediated CCL5 production in keratinocytes. HintergrundToll-Like Rezeptor 2 (TLR2) der Keratinozyten kann durch Staphylococcus spp. aktiviert werden, der auf der Haut von Hunden mit atopischer Dermatitis (AD) h & auml;ufig gefunden werden kann. Man geht davon aus, dass C-C Chemokin-Ligand-5 (CCL5), welches von Keratinozyen produziert wird, bei der Pathogenese der caninen AD (cAD) eine Rolle spielt. Es bleibt jedoch unklar, ob die CCL5 Produktion durch TLR2 Aktivierung in den Keratinozyten des Hundes induziert wird.Hypothese/ZieleDas Ziel war es die Wirksamkeit von TLR2 Agonisten auf die CCL5 Produktion in caninen Keratinozyten, sowie eine m & ouml;gliche Synergie mit Interferon (IFN)-gamma, Interleukin (IL)-13 oder IL-4 und zugrundeliegende Mechanismen zu beleuchten.Materialien und MethodenEs wurden canine epidermale Keratinozyten Stammzellen (CPEK) mittels TLR2 Agonisten mit oder ohne Inhibitoren des TLR2 Signalwegs oder IFN-gamma, einem T-Helferzell (Th)1-Typ Zytokin und/oder IL-13 oder IL-4, einem Th2-Typ Zytokin stimuliert. Die CCL5 Proteinkonzentrationen im & Uuml;berstand der Kultur wurden mittels Enzym-linked Immunosorbent Assay gemessen. Zus & auml;tzlich wurde die TLR2 mRNA Exprimierung mittels Real-Time PCR in mit IFN-gamma stimulierten CPEK-Zellen gemessen.ErgebnisseDie TLR2 Agonisten erh & ouml;hten die CCL5 Produktion in CPEK-Zellen. Die Inhibitoren des TLR2 Signalwegs unterdr & uuml;ckten die CCL5 Produktion. IFN-gamma, jedoch weder IL-13 noch IL-4 erh & ouml;hten synergistisch die durch TLR2 Agonisten-induzierte CCL5 Produktion. IFN-gamma erh & ouml;hte teilweise die TLR2 mRNA Exprimierung in CPEK Zellen.Schlussfolgerungen und klinische BedeutungEine TLR2 Aktivierung durch Staphylococcus spp. k & ouml;nnte CCL5 in caninen Keratinozyten produzieren, wobei Immunzellen in die Haut von Hunden mit AD rekrutiert werden. W & auml;hrend der Th1-aktivierten chronischen Phase der cAD, in der die TLR2 Exprimierung teilweise hochreguliert sein k & ouml;nnte, kann Staphylococcus spp. die Hautentz & uuml;ndung verst & auml;rken. Es sind weitere Studien n & ouml;tig, um die klinische Bedeutung und die Mechanismen der durch Hautbakterien mediierten CCL5 Produktion in Keratinozyten zu ermitteln. (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic) Toll (sic)(sic)(sic) 2 (TLR2) (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic), (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic) (AD) (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic) C-C (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic) 5 (CCL5) (sic)(sic)(sic)(sic)(sic) AD (cAD) (sic)(sic)(sic)(sic)(sic)(sic)(sic).(sic)(sic), TLR2 (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic) CCL5 (sic)(sic)(sic)(sic)(sic)(sic)(sic).(sic)(sic)/(sic)(sic)(sic)(sic) TLR2 (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic) CCL5 (sic)(sic)(sic)(sic)(sic), (sic)(sic)(sic)(sic)(sic)(sic) (IFN)-gamma,(sic)(sic)(sic)(sic)(sic) (IL)-13 (sic) IL-4 (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).(sic)(sic)(sic)(sic)(sic)(sic) TLR2 (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic) (CPEK), (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic) TLR2 (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic) IFN-gamma((sic)(sic) T (sic)(sic) (Th)1 (sic)(sic)(sic)(sic)(sic))(sic)/(sic) IL-13 (sic) IL-4((sic)(sic) Th2 (sic)(sic)(sic)(sic)(sic)).(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic) CCL5 (sic)(sic)(sic)(sic).(sic)(sic), (sic)(sic)(sic)(sic) PCR (sic)(sic)(sic) IFN-gamma (sic)(sic)(sic) CPEK (sic)(sic)(sic)(sic) TLR2 mRNA (sic)(sic).(sic)(sic)TLR2 (sic)(sic)(sic)(sic)(sic)(sic) CPEK (sic)(sic)(sic)(sic) CCL5 (sic)(sic).TLR2 (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic) CCL5 (sic)(sic)(sic).IFN-gamma((sic)(sic) IL-13 (sic) IL-4)(sic)(sic)(sic)(sic)(sic) TLR2 (sic)(sic)(sic)(sic)(sic)(sic) CCL5 (sic)(sic).IFN-gamma (sic)(sic)(sic)(sic)(sic) CPEK (sic)(sic)(sic)(sic) TLR2 mRNA (sic)(sic).(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic) TLR2 (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic) CCL5, (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic) AD (sic)(sic)(sic)(sic)(sic)(sic).(sic) Th1 (sic)(sic)(sic) cAD (sic)(sic)(sic), TLR2 (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic), (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic) CCL5 (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic). ContexteLe r & eacute;cepteur Toll-like 2 (TLR2) dans les k & eacute;ratinocytes peut & ecirc;tre activ & eacute; par Staphylococcus spp. fr & eacute;quemment d & eacute;tect & eacute; sur la peau des chiens atteints de dermatite atopique (DA). Le ligand 5 de la chimiokine & agrave; motif C-C (CCL5) produit par les k & eacute;ratinocytes est consid & eacute;r & eacute; comme impliqu & eacute; dans la pathog & eacute;nie de la dermatite atopique canine (DAC). Cependant, on ne sait toujours pas si l'activation du TLR2 induit la production de CCL5 dans les k & eacute;ratinocytes canins.Hypoth & egrave;se/objectifs & Eacute;lucider l'effet des agonistes TLR2 sur la production de CCL5 dans les k & eacute;ratinocytes canins, la synergie possible avec l'interf & eacute;ron (IFN)-gamma, l'interleukine (IL)-13 ou l'IL-4, et les m & eacute;canismes sous-jacents.Mat & eacute;riels et m & eacute;thodesDes cellules prog & eacute;nitrices de k & eacute;ratinocytes & eacute;pidermiques canins (CPEK) sont stimul & eacute;es avec des agonistes TLR2 avec ou sans inhibiteurs de la voie de signalisation TLR2 ou IFN-gamma, une cytokine de type T-helper (Th)1, et/ou IL-13 ou IL-4, une cytokine de type Th2. Les concentrations de prot & eacute;ines CCL5 dans le surnageant de culture sont mesur & eacute;es par dosage immuno-enzymatique. De plus, l'expression de l'ARNm TLR2 est mesur & eacute;e par PCR en temps r & eacute;el dans les cellules CPEK stimul & eacute;es par l'IFN-gamma.R & eacute;sultatsLes agonistes du TLR2 augmentent la production de CCL5 dans les cellules CPEK. Les inhibiteurs de la voie de signalisation TLR2 suppriment la production de CCL5. L'IFN-gamma, mais pas l'IL-13 ou l'IL-4, augmente de mani & egrave;re synergique la production de CCL5 induite par les agonistes TLR2. L'IFN-gamma augmente partiellement l'expression de l'ARNm de TLR2 dans les cellules CPEK.Conclusions et pertinence cliniqueL'activation de TLR2 par Staphylococcus spp. peut produire du CCL5 dans les k & eacute;ratinocytes canins, recrutant ainsi des cellules immunitaires dans la peau des chiens atteints de DAC. Pendant la phase chronique activ & eacute;e par Th1 de la DAC, o & ugrave; l'expression de TLR2 peut & ecirc;tre partiellement r & eacute;gul & eacute;e & agrave; la hausse, Staphylococcus spp. peut exacerber l'inflammation cutan & eacute;e. D'autres & eacute;tudes sont n & eacute;cessaires pour d & eacute;terminer la signification clinique et les m & eacute;canismes de la production de CCL5 par les bact & eacute;ries cutan & eacute;es dans les k & eacute;ratinocytes. (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)Toll-like receptor 2(TLR2)(sic),(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(AD)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)C-C(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)5(CCL5)(sic)(sic)AD(cAD)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).(sic)(sic)(sic)(sic)(sic)(sic),(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)TLR2(sic)(sic)(sic)(sic)(sic)CCL5(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).(sic)(sic)/(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic),(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)CCL5(sic)(sic)(sic)(sic)(sic)(sic)TLR2(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic),(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(IFN)-gamma,(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(IL)-13(sic)(sic)(sic)IL-4(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic),(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(CPEK)(sic)(sic)(sic),TLR2(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic),(sic)(sic)(sic)T(sic)(sic)(sic)(sic)(Th)1(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)IFN-gamma,(sic)(sic)(sic)/(sic)(sic)(sic)Th2(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)IL-13(sic)(sic)(sic)IL-4(sic)(sic)(sic)(sic)(sic)TLR2(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).(sic)(sic)(sic)(sic)(sic)(sic)CCL5(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic),(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).(sic)(sic)(sic),IFN-gamma(sic)(sic)(sic)(sic)(sic)CPEK(sic)(sic)(sic)TLR2 mRNA(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)PCR(sic)(sic)(sic)(sic)(sic)(sic).(sic)(sic)TLR2(sic)(sic)(sic)(sic)(sic)(sic)CPEK(sic)(sic)(sic)(sic)(sic)(sic)CCL5(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).TLR2(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)CCL5(sic)(sic)(sic)(sic)(sic)(sic)(sic).IL-13(sic)IL-4(sic)(sic)(sic)(sic),IFN-gamma(sic)TLR2(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)CCL5(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).IFN-gamma(sic),CPEK(sic)(sic)(sic)TLR2 mRNA(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)TLR2(sic)(sic)(sic)(sic),(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)CCL5(sic)(sic)(sic)(sic),(sic)(sic)(sic)(sic)(sic)(sic)AD(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).TLR2(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)cAD(sic)Th1(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic),(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)CCL5(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic),(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic). ContextoO receptor Toll-like 2 (TLR2) em queratin & oacute;citos pode ser ativado por Staphylococcus spp., que s & atilde;o frequentemente detectados na pele de c & atilde;es com dermatite at & oacute;pica (DA). O envolvimento do ligante de quimiocina do motivo C-C 5 (CCL5) produzido por queratin & oacute;citos na patog & ecirc;nese da DA canina (CAD) tem sido considerado. No entanto, se a ativa & ccedil;& atilde;o do TLR2 induz a produ & ccedil;& atilde;o de CCL5 em queratin & oacute;citos caninos ainda n & atilde;o est & aacute; claro.Hip & oacute;tese/ObjetivosElucidar o efeito dos agonistas do TLR2 na produ & ccedil;& atilde;o de CCL5 em queratin & oacute;citos caninos, poss & iacute;vel sinergia com interferon (IFN)-gamma, interleucina (IL)-13 ou IL-4 e mecanismos subjacentes.Materiais e m & eacute;todosC & eacute;lulas de queratin & oacute;citos epid & eacute;rmicos progenitores caninos (CPEK) foram estimuladas com agonistas de TLR2 com ou sem inibidores da via de sinaliza & ccedil;& atilde;o de TLR2 ou IFN-gamma, uma citocina do tipo T-helper (Th)1, e/ou IL-13 ou IL-4, uma citocina do tipo Th2. As concentra & ccedil;& otilde;es de prote & iacute;na CCL5 no sobrenadante da cultura foram medidas por ensaio imunoenzim & aacute;tico. Al & eacute;m disso, a express & atilde;o de mRNA de TLR2 foi medida por PCR em tempo real em c & eacute;lulas CPEK estimuladas com IFN-gamma.ResultadosOs agonistas de TLR2 aumentaram a produ & ccedil;& atilde;o de CCL5 em c & eacute;lulas CPEK. J & aacute; os inibidores da via de sinaliza & ccedil;& atilde;o de TLR2 suprimiram a produ & ccedil;& atilde;o de CCL5. IFN-gamma, mas n & atilde;o IL-13 ou IL-4, aumentaram sinergicamente a produ & ccedil;& atilde;o de CCL5 induzida por agonista de TLR2. IFN-gamma aumentou parcialmente a express & atilde;o de mRNA de TLR2 em c & eacute;lulas CPEK.Conclus & otilde;es e relev & acirc;ncia cl & iacute;nicaA ativa & ccedil;& atilde;o de TLR2 por Staphylococcus spp. pode produzir CCL5 em queratin & oacute;citos caninos, recrutando assim c & eacute;lulas imunes para a pele de c & atilde;es com DA. Durante a fase cr & ocirc;nica ativada por Th1 da DAC, onde a express & atilde;o de TLR2 pode ser parcialmente regulada positivamente, Staphylococcus spp. pode exacerbar a inflama & ccedil;& atilde;o da pele. Estudos adicionais s & atilde;o necess & aacute;rios para determinar a signific & acirc;ncia cl & iacute;nica e os mecanismos da produ & ccedil;& atilde;o de CCL5 mediada por bact & eacute;rias da pele em queeratin & oacute;citos. Introducci & oacute;nEl receptor tipo Toll 2 (TLR2) en los queratinocitos puede ser activado por Staphylococcus spp., que se detectan con frecuencia en la piel de perros con dermatitis at & oacute;pica (AD). Se ha considerado que el ligando 5 de quimioquina con motivo C-C (CCL5) producido por los queratinocitos est & aacute; involucrado en la patog & eacute;nesis de la AD canina (cAD). Sin embargo, a & uacute;n no est & aacute; claro si la activaci & oacute;n de TLR2 induce la producci & oacute;n de CCL5 en los queratinocitos caninos.Hip & oacute;tesis/ObjetivosDilucidar el efecto de los agonistas de TLR2 en la producci & oacute;n de CCL5 en los queratinocitos caninos, la posible actividad sin & eacute;rgica con el interfer & oacute;n (IFN)-gamma, la interleuquina (IL)-13 o IL-4 y los mecanismos subyacentes.Materiales y m & eacute;todosSe estimularon c & eacute;lulas progenitoras de queratinocitos epid & eacute;rmicos caninos (CPEK) con agonistas de TLR2 con o sin inhibidores de la v & iacute;a de se & ntilde;alizaci & oacute;n de TLR2 o IFN-gamma, una citoquina de tipo T-helper (Th)1, y/o IL-13 o IL-4, una citocina de tipo Th2. Las concentraciones de prote & iacute;na CCL5 en el sobrenadante de cultivo se midieron mediante un ensayo inmunoabsorbente ligado a enzimas. Adem & aacute;s, se midi & oacute; la expresi & oacute;n de RNAm de TLR2 mediante PCR en tiempo real en c & eacute;lulas CPEK estimuladas con IFN-gamma.ResultadosLos agonistas de TLR2 aumentaron la producci & oacute;n de CCL5 en c & eacute;lulas CPEK. Los inhibidores de la v & iacute;a de se & ntilde;alizaci & oacute;n de TLR2 suprimieron la producci & oacute;n de CCL5. El IFN-gamma, pero no la IL-13 o la IL-4, mejoraron sin & eacute;rgicamente la producci & oacute;n de CCL5 inducida por agonistas de TLR2. El IFN-gamma aument & oacute; parcialmente la expresi & oacute;n de RNAm de TLR2 en c & eacute;lulas CPEK.Conclusiones y relevancia cl & iacute;nicaLa activaci & oacute;n de TLR2 por Staphylococcus spp. puede producir CCL5 en los queratinocitos caninos, reclutando as & iacute; c & eacute;lulas immunes en la piel de los perros con AD. Durante la fase cr & oacute;nica de la cAD activada por Th1, donde la expresi & oacute;n de TLR2 puede estar parcialmente regulada al alza, Staphylococcus spp. puede exacerbar la inflamaci & oacute;n de la piel. Se requieren estudios adicionales para determinar la importancia cl & iacute;nica y los mecanismos de la producci & oacute;n de CCL5 mediada por bacterias de la piel en los queratinocitos.
2025年04月, 研究論文(学術雑誌), 共同, 36, 2, 0959-4493,
DOI(公開)(r-map), 117, 126