Agonist Of Adenosine A2A Receptor Ameliorates Dextran Sulfate Sodium-induced Colitis In Mice

Background:Ulcerative colitis(UC), one type of inflammatory bowel disease(IBD), is characterized by uncontrolled inflammation in the colon and rectum. Conventional therapies for UC fail to successfully induce remission and prevent relapse, and also possibly cause various side effects. Therefore, exploring the novel therapies for UC has become a topic of great interest. Recently, adenosine A2 A receptor has been shown to exhibit anti-inflammatory and immuno-suppressive effects. However, it still remains to be elucidated how adenosine A2 A receptor regulates inflammatory responses in colon, as seen in murine colitis.Objective:To explore the pivotal role of adenosine A2 A receptor in regulation of inflammatory responses in murine dextran sulfate sodium(DSS)-induced colitis.Methods:Balb/c mice were randomly divided into 4 groups: Control, DSS, DSS+CGS21680, DSS+CSC. The mice were fed with 4% DSS(w/v) solution from day 1 to day 7 to induce acute colitis. The groups of DSS+CGS21680, DSS+CSC were administered intraperitoneally CGS21680 1mg/kg or CSC 2.5mg/kg since day 3 to day 7. Disease activity index(DAI) was recorded daily until day 7. The expressions of CD68, p NF-κB p65, MPO activity, and TNF, IL-1β level in inflamed colon of each group were measured.Results:1. On day 7, the DAI of DSS+CGS21680(1.57±0.65) is significantly lower than DSS(3.10±0.47) and DSS+CSC(3.07±0.21)(P<0.05);The DAI of control is 0.2. The histological score of DSS+CGS21680(1.80±0.79) is significantly lower than group DSS(3.10±0.74)and DSS+CSC(3.00±0.82)(P<0.05), while each groups are higher than control(0)(P <0.05).3. The MPO activity in colonic tissue of group DSS( 9.91±1.66 U/g) and DSS+CSC(10.96±1.28U/g) are significantly higher than group DSS+CGS21680(7.72±0.67U/g)(P<0.05).4. The level of TNF in colonic tissue of group DSS(270.77±57.55pg/g) and DSS+CSC(265.88±69.35pg/g) are significantly higher than group DSS+CGS21680(138.47±40.46pg/g)(P<0.05).5. The levels of IL-1β in colonic tissue of group DSS(176.88±55.84pg/g) and DSS+CSC(196.52±47.80pg/g) are significantly higher than group control and DSS+CGS21680(54.71±36.22pg/g)(P<0.05).6. The number of p NF-κB p65 positive cells in mucosa of DSS+CGS21680group is significantly lower than the groups of DSS and DSS+CSC(P<0.05), higher than control group(P<0.05).7. The number of CD68 positive cells in mucosa of DSS+CGS21680 group is significantly lower than the DSS group and DSS+CSC group(P<0.05), higher than control group(P<0.05).Conclusion:Agonist of adenosine A2 A receptor ameliorates DSS induced colitis in mice, by inhibiting infiltration of macrophage to the lamino propria and down-regulating NF-κB activation.