TY - JOUR
T1 - Amniotic membrane modulates innate immune response inhibiting PRRs expression and NF-κB nuclear translocation on limbal myofibroblasts
AU - Alfredo, Domínguez López
AU - Victor Manuel, Bautista de Lucio
AU - Janet, Serafín López
AU - Edson, Robles Sánchez
AU - Yonathan, Garfias
N1 - Funding Information:
This work was supported by CONACYT SALUD - 160286 and SEP - 167438 grants and CVU : 406706 ; DGAPA UNAM-PAPIIT IA203514 and “ Conde de Valenciana ” Foundation.
PY - 2014/10
Y1 - 2014/10
N2 - Corneal damage observed in a viral infection such as herpetic stromal keratitis is mainly caused by proinflammatory molecules released by resident cells in the response to viral antigens. There are pattern recognition receptors like MDA5, RIG-1, and TLR3, that recognize viral dsRNA and after activation, the innate immune response is exacerbated inducing the synthesis and secretion of inflammatory cytokines through NF-κB activation. Amniotic membrane (AM) has demonstrated to reduce inflammation by several mechanisms, however the effect of AM on innate immune receptors such as MDA5, RIG-1, and TLR3 has not been reported. In this study, we have determined that the presence of AM significantly inhibited the synthesis and secretion of proinflammatory cytokines on human limbal myofibroblasts (HLM) stimulated with poly I:C. Similarly, the presence of AM reduced the protein expression of MDA5, RIG-1, and TLR3 on poly I:C stimulated HLM. Additionally, the presence of the AM significantly inhibited the NF-κB nuclear translocation when the HLM were poly I:C stimulated, and concomitantly, the AM was able to relocate cadherins affecting the myofibroblastic cellular morphology. These results suggest that AM generates an anti-inflammatory microenvironment, and specific inhibition of NFκB nuclear translocation on infected corneal tissue would reduce the inflammation undesirable effects, explaining in part the beneficial usefulness of transplanting AM on herpetic stromal keratitis.
AB - Corneal damage observed in a viral infection such as herpetic stromal keratitis is mainly caused by proinflammatory molecules released by resident cells in the response to viral antigens. There are pattern recognition receptors like MDA5, RIG-1, and TLR3, that recognize viral dsRNA and after activation, the innate immune response is exacerbated inducing the synthesis and secretion of inflammatory cytokines through NF-κB activation. Amniotic membrane (AM) has demonstrated to reduce inflammation by several mechanisms, however the effect of AM on innate immune receptors such as MDA5, RIG-1, and TLR3 has not been reported. In this study, we have determined that the presence of AM significantly inhibited the synthesis and secretion of proinflammatory cytokines on human limbal myofibroblasts (HLM) stimulated with poly I:C. Similarly, the presence of AM reduced the protein expression of MDA5, RIG-1, and TLR3 on poly I:C stimulated HLM. Additionally, the presence of the AM significantly inhibited the NF-κB nuclear translocation when the HLM were poly I:C stimulated, and concomitantly, the AM was able to relocate cadherins affecting the myofibroblastic cellular morphology. These results suggest that AM generates an anti-inflammatory microenvironment, and specific inhibition of NFκB nuclear translocation on infected corneal tissue would reduce the inflammation undesirable effects, explaining in part the beneficial usefulness of transplanting AM on herpetic stromal keratitis.
KW - Amniotic membrane
KW - Inflammatory cytokines
KW - Limbal myofibroblasts
KW - MDA-5
KW - RIG-1
KW - TLR-3
UR - http://www.scopus.com/inward/record.url?scp=84907328654&partnerID=8YFLogxK
U2 - 10.1016/j.exer.2014.08.002
DO - 10.1016/j.exer.2014.08.002
M3 - Artículo
C2 - 25117451
AN - SCOPUS:84907328654
SN - 0014-4835
VL - 127
SP - 215
EP - 223
JO - Experimental Eye Research
JF - Experimental Eye Research
ER -