Enteric glial-derived S100B protein stimulates nitric oxide production in celiac disease.
OBJECTIVE
Enteric glia participates to the homeostasis of the gastrointestinal tract. In the central nervous system, increased expression of astroglial-derived S100B protein has been associated with the onset and maintaining of inflammation. The role of enteric glial-derived S100B protein in gastrointestinal inflammation has never been investigated in humans. In this study, we evaluated the expression of S100B and its relationship with nitric oxide production in celiac disease.


METHODS
Duodenal biopsy specimens from untreated and on gluten-free diet patients with celiac disease and controls were respectively processed for S100B and inducible nitric oxide synthase (iNOS) protein expression and nitrite production. To evaluate the direct involvement of S100B in the inflammation, control biopsy specimens were exposed to exogenous S100B, and iNOS protein expression and nitrite production were measured. We also tested gliadin induction of S100B-dependent inflammation in cultured biopsy specimens deriving from on gluten-free diet patients in the absence or presence of the specific S100B antibody.


RESULTS
S100B messenger RNA and protein expression, iNOS protein expression, and nitrite production were significantly increased in untreated patients but not in on gluten-free diet patients vs controls. Addition of S100B to control biopsy specimens resulted in a significant increase of iNOS protein expression and nitrite production. In celiac disease patients but not in controls biopsy specimens, gliadin challenge significantly increased S100B messenger RNA and protein expression, iNOS protein expression, and nitrite production, but these effects were completely inhibited by S100B antibody.


CONCLUSIONS
Enteric glial-derived S100B is increased in the duodenum of patients with celiac disease and plays a role in nitric oxide production.
Department of Experimental Pharmacology, University Federico II, Naples, Italy.
Giuseppe
G
Esposito
Carla
C
Cirillo
Giovanni
G
Sarnelli
Daniele
D
De Filippis
Francesco Paolo
FP
D'Armiento
Alba
A
Rocco
Gerardo
G
Nardone
Raffaella
R
Petruzzelli
Michela
M
Grosso
Paola
P
Izzo
Teresa
T
Iuvone
Rosario
R
Cuomo
D000328:Adult; D000368:Aged; D001253:Astrocytes / Q000378:metabolism*; D001706:Biopsy; D016022:Case-Control Studies; D002446:Celiac Disease / Q000378:metabolism* / Q000473:pathology; D004386:Duodenum / Q000294:innervation / Q000378:metabolism* / Q000473:pathology; D005903:Gliadin / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
D009414:Nerve Growth Factors; D009573:Nitrites; D012333:RNA, Messenger; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D009569:Nitric Oxide; D005903:Gliadin; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases