Loperamide-induced Constipation activates Inflammatory Signaling Pathways in the Transverse Colon of SD rats via Complement C3 and its receptors.
BACKGROUND
Complement component 3 (C3) receptors play an important role as an inflammatory mediator in the innate immune system, although their mechanism was not well studied during constipation.


OBJECTIVE
The aim of this study is to investigate the regulatory role of C3 and its receptors' downstream signaling during constipation.


METHODS
Alterations in the C3, C3a receptor (C3aR), and C3b receptor (C3bR) expressions, PI3K/AKT pathway, RhoA/MLC pathway, MAP kinase pathway, and inflammatory cytokine expressions were measured in the transverse colon of loperamide (Lop) treated SD rats.


RESULTS
Lop treatment successfully induced constipation phenotypes, including decreased stool parameters and histological structure alterations. The expression levels of C3 were significantly increased, whereas expressions of C3aR and C3bR were observed to decrease during Lop-induced constipation. Moreover, significant upregulation was observed in the phosphorylation levels of PI3K, AKT, and GSK3 in transverse colons of Lop treated SD rats. The expression of RhoA and phosphorylation of MLC were also enhanced in the Lop treated group. Furthermore, a similar pattern was detected in the MAP kinase pathway and inflammatory cytokine expressions. Subsequent to Lop treatment, the phosphorylation of ERK and p38, as well as the mRNA levels of NF-κB, TNF-α, IL-6 and IL-1α were remarkably increased in the transverse colon.


CONCLUSION
These results indicate that Lop-induced constipation is tightly linked to the downregulation of C3aR and C3bR expressions and upregulation of the C3, C3Rs downstream signaling pathway, including PI3K/AKT, RhoA/MLC, and MAP kinase pathways as well as inflammatory cytokine expressions in the transverse colon of SD rats.</P>.
['Choi|Yun Ju|YJ|', 'Kim|Ji Eun|JE|', 'Lee|Su Jin|SJ|', 'Gong|Jeong Eun|JE|', 'Jang|Miran|M|', 'Hong|Jin Tae|JT|', 'Hwang|Dae Youn|DY|']
Constipation Complement C3 C3a receptor C3b receptor PI3K/AKT pathway Loperamide