TY - JOUR
T1 - MicroRNA-132 modulates cholinergic signaling and inflammation in human inflammatory bowel disease
AU - Maharshak, Nitsan
AU - Shenhar-Tsarfaty, Shani
AU - Aroyo, Nimrod
AU - Orpaz, Naama
AU - Guberman, Irene
AU - Canaani, Jonathan
AU - Halpern, Zamir
AU - Dotan, Iris
AU - Berliner, Shlomo
AU - Soreq, Hermona
PY - 2013/6
Y1 - 2013/6
N2 - Background: MicroRNA-132 (miR-132) targets acetylcholinesterase (AChE) and potentiates the cholinergic blockade of inflammatory reactions in cultured cells and experimental mice, but the implications of this interaction to human inflammatory disease remained unexplored. This study aimed to test whether miR-132 is causally involved in anti-inflammatory reactions of patients with inflammatory bowel disease (IBD) and modulates vagal tone and consequently inflammation in patients with IBD. Methods: We prospectively measured inflammation readouts and the cholinergic status (total capacity for hydrolyzing acetylcholine in one's circulation), and AChE activity in 2 independent cohorts of patients with IBD and quantified miR-132 levels in intestinal tissue biopsies removed at colonoscopy from inflamed and apparently quiescent tissues of tested volunteers. Results: MiR-132 levels are higher in inflamed compared with apparently quiescent intestinal biopsies from patients with IBD. Correspondingly, the cholinergic status and AChE activity was significantly lower in patients with IBD suffering from moderate-severe disease as compared with healthy controls or patient with IBD presenting low disease severity. Patients with IBD (n = 16) presented lower AChE activity compared with healthy controls (n = 33;289 6 128 AU versus 391 6 102 AU, P = 0.001), and a negative correlation between AChE activity and C-reactive protein levels (r = 20.47, P = 0.01). Corroborating these observations in an additional cohort of participants, C-reactive protein and AChE activity were negatively correlated in patients with moderate-severe disease (n = 16; r = 20.6, P = 0.04) and positively correlated in healthy controls (n = 74, r = 0.24, P = 0.046). Conclusions: Taken together, these findings support an inflammation-dependent homeostatic role for the regulation by miR-132 of AChE in IBD, opening new venues for therapeutic interference.
AB - Background: MicroRNA-132 (miR-132) targets acetylcholinesterase (AChE) and potentiates the cholinergic blockade of inflammatory reactions in cultured cells and experimental mice, but the implications of this interaction to human inflammatory disease remained unexplored. This study aimed to test whether miR-132 is causally involved in anti-inflammatory reactions of patients with inflammatory bowel disease (IBD) and modulates vagal tone and consequently inflammation in patients with IBD. Methods: We prospectively measured inflammation readouts and the cholinergic status (total capacity for hydrolyzing acetylcholine in one's circulation), and AChE activity in 2 independent cohorts of patients with IBD and quantified miR-132 levels in intestinal tissue biopsies removed at colonoscopy from inflamed and apparently quiescent tissues of tested volunteers. Results: MiR-132 levels are higher in inflamed compared with apparently quiescent intestinal biopsies from patients with IBD. Correspondingly, the cholinergic status and AChE activity was significantly lower in patients with IBD suffering from moderate-severe disease as compared with healthy controls or patient with IBD presenting low disease severity. Patients with IBD (n = 16) presented lower AChE activity compared with healthy controls (n = 33;289 6 128 AU versus 391 6 102 AU, P = 0.001), and a negative correlation between AChE activity and C-reactive protein levels (r = 20.47, P = 0.01). Corroborating these observations in an additional cohort of participants, C-reactive protein and AChE activity were negatively correlated in patients with moderate-severe disease (n = 16; r = 20.6, P = 0.04) and positively correlated in healthy controls (n = 74, r = 0.24, P = 0.046). Conclusions: Taken together, these findings support an inflammation-dependent homeostatic role for the regulation by miR-132 of AChE in IBD, opening new venues for therapeutic interference.
KW - Acetylcholinesterase
KW - Cholinergic status
KW - Colitis
KW - MicroRNA
KW - Vagal tone
UR - http://www.scopus.com/inward/record.url?scp=84879073845&partnerID=8YFLogxK
U2 - 10.1097/MIB.0b013e318281f47d
DO - 10.1097/MIB.0b013e318281f47d
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C2 - 23598815
AN - SCOPUS:84879073845
SN - 1078-0998
VL - 19
SP - 1346
EP - 1353
JO - Inflammatory Bowel Diseases
JF - Inflammatory Bowel Diseases
IS - 7
ER -