Effects of Osthole on Inflammatory Gene Expression and Cytokine Secretion in Histamine-Induced Inflammation in the Caco-2 Cell Line.

Natalia K Kordulewska,Beata Jarmołowska,Justyna Topa,Dominika Rozmus

doi:10.3390/ijms222413634

Abstract

Hyperactivity of the immune system in the gastrointestinal tract leads to the development of chronic, inflammation-associated disorders. Such diseases, including inflammatory bowel disease, are not completely curable, but the specific line of treatment may reduce its symptoms. However, the response to treatment varies among patients, creating a necessity to uncover the pathophysiological basis of immune-mediated diseases and apply novel therapeutic strategies. The present study describes the anti-inflammatory properties of osthole during histamine-induced inflammation in the intestinal Caco-2 cell line. Osthole reduced the secretion of cytokines (CKs) and the expression level of inflammation-associated genes, which were increased after a histamine treatment. We have shown that the secretion of pro-inflammatory CKs (IL-1β, IL-6, IL-8, and TNF-α) during inflammation may be mediated by NFκB, and, after osthole treatment, this signaling pathway was disrupted. Our results suggest a possible role for osthole in the protection against inflammation in the gastrointestinal tract; thus, osthole may be considered as an anti-inflammatory modulator.

Highlights

Excessive inflammation in the gastrointestinal tract leads to the development of inflammatory bowel disease (IBD), which is a chronic gastrointestinal disorder [1]
This trend continued until 48 h of incubation with three out of four doses of histamine (100 ng/mL—p = 0.01, 150 ng/mL—p < 0.01, 200 ng/mL—p < 0.0001) and its mixtures with FXF and osthole (p < 0.001, for both), where proliferation was significantly higher compared to the control (Figure 2A,B)
The secretion of IL-4, IL-10, and IL-13 tended to negatively correlate with the IL-8 secretion, partially confirming the results described by Lügering et al IL-8 plays an important role in acute and chronic processes, while IL-4 and-13 are down regulated in the inflammatory response [52]

Summary

Introduction

Excessive inflammation in the gastrointestinal tract leads to the development of inflammatory bowel disease (IBD), which is a chronic gastrointestinal disorder [1]. The symptoms of the disease can be reduced by using appropriate pharmacological agents, but IBD is not fully curable [2,3,4,5,6]. Two main types of IBD can be distinguished: ulcerative colitis (UC) and Crohn’s disease (CD). Increasing knowledge of the pathophysiology of immune-mediated diseases has led to the development of targeted therapies that can selectively interfere with the crucial mediators of the inflammatory process [9,10,11,12]

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Conclusion