Submit Manuscript  

Article Details


Loperamide-induced Constipation Activates Inflammatory Signaling Pathways in the Mid Colon of SD Rats Via Complement C3 and its Receptors

Author(s):

Yun Ju Choi, Ji Eun Kim, Su Jin Lee, Jeong Eun Gong, Miran Jang, Jin Tae Hong and Dae Youn Hwang*   Pages 1 - 12 ( 12 )

Abstract:


Background: Complement component 3 (C3) receptors play an important role as inflammatory mediators in the innate immune system, although their mechanisms were 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 mid 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 decreased during Lop-induced constipation. Moreover, significant upregulation was observed in the phosphorylation levels of PI3K, AKT, and GSK3β in mid 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 the 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 mid 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 and C3Rs downstream signaling pathway, including PI3K/AKT, RhoA/MLC, and MAP kinase pathways as well as inflammatory cytokine expressions in the mid colon of SD rats.

Keywords:

Complement C3, Constipation, C3a receptor, C3b receptor, PI3K/AKT pathway, Loperamide.

Affiliation:

Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, College of Pharmacy, Chungbuk National University, Cheongju 28159, Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463



Read Full-Text article