Grim19 Attenuates DSS Induced Colitis in an Animal Model

Jae-Kyung Kim; Seung Hoon Lee; Seon-Young Lee; Eun-Kyung Kim; Jeong-Eun Kwon; Hyeon-Beom Seo; Han Hee Lee; Bo-In Lee; Sung-Hwan Park; Mi-La Cho

doi:10.1371/journal.pone.0155853

Grim19 Attenuates DSS Induced Colitis in an Animal Model

PLoS One. 2016 Jun 3;11(6):e0155853. doi: 10.1371/journal.pone.0155853. eCollection 2016.

Authors

Jae-Kyung Kim^{1

2}, Seung Hoon Lee^{1

2}, Seon-Young Lee^{1

2}, Eun-Kyung Kim^{1

2}, Jeong-Eun Kwon^{1

2}, Hyeon-Beom Seo^{1

2}, Han Hee Lee³, Bo-In Lee³, Sung-Hwan Park^{1

4}, Mi-La Cho^{1

2}

Affiliations

¹ The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-701, South Korea.
² Laboratory of Immune Network, Catholic Research Institute of Medical Science, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-701, South Korea.
³ Division of Gastroenterlogy, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
⁴ Division of Rheumatology, Department of Internal Medicine, The Catholic University of Korea, Seoul, 137-040, South Korea.

Abstract

DSS induced colitis is a chronic inflammatory disease characterized by inflammation in the gastrointestinal tract, which destabilizes the gut and induces an uncontrolled immune response. Although DSS induced colitis is generally thought to develop as a result of an abnormally active intestinal immune system, its pathogenesis remains unclear. Gene associated with retinoid interferon induced mortality (Grim) 19 is an endogenous specific inhibitor of STAT3, which regulates the expression of proinflammatory cytokines. In this study, we investigated the influence of GRIM19 in a DSS induced colitis mouse model. We hypothesized that Grim19 would ameliorate DSS induced colitis by altering STAT3 activity and intestinal inflammation. Grim19 ameliorated DSS induced colitis severity and protected intestinal tissue. The expression of STAT3 and proinflammatory cytokines such as IL-1β and TNF-α in colon and lymph nodes was decreased significantly by Grim19. Moreover, DSS induced colitis progression in a Grim19 transgenic mouse line was inhibited in association with a reduction in STAT3 and IL-17 expression. These results suggest that Grim19 attenuates DSS induced colitis by suppressing the excessive inflammatory response mediated by STAT3 activation.

MeSH terms

Animals
Colitis / chemically induced
Colitis / genetics
Colitis / metabolism*
Colitis / pathology
Colon / metabolism*
Colon / pathology
Dextran Sulfate
Disease Models, Animal
Inflammation / metabolism
Inflammation / pathology
Interleukin-17 / metabolism
Interleukin-1beta / metabolism
Lymph Nodes / metabolism*
Lymph Nodes / pathology
Mice
Mice, Inbred C57BL
Mice, Transgenic
NADH, NADPH Oxidoreductases / genetics
NADH, NADPH Oxidoreductases / metabolism*
STAT3 Transcription Factor / metabolism
Tumor Necrosis Factor-alpha / metabolism

Substances

Interleukin-17
Interleukin-1beta
STAT3 Transcription Factor
Tumor Necrosis Factor-alpha
Dextran Sulfate
NADH, NADPH Oxidoreductases
Grim19 protein, mouse

Grants and funding

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (https://www.khidi.or.kr/) (HI15C1062). This study was also supported by a grant of the Korean Health Technology R&D Project, Ministry for Health & Welfare, Republic of Korea (HI14C3417); and a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI13C0016).