Increased Cerebral Tff1 Expression in Two Murine Models of Neuroinflammation.
OBJECTIVE
The trefoil factor family (TFF) peptide TFF1 is a typical secretory product of the gastric mucosa and a very low level of expression occurs in nearly all regions of the murine brain. TFF1 possesses a lectin activity and binding to a plethora of transmembrane glycoproteins could explain the diverse biological effects of TFF1 (e.g., anti-apoptotic effect). It was the aim to test whether TFF expression is changed during neuroinflammation.


METHODS
Expression profiling was performed using semi-quantitative RT-PCR analyses in two murine models of neuroinflammation, i.e. Toxoplasma gondii-induced encephalitis and experimental autoimmune encephalomyelitis (EAE), the latter being the most common animal model of multiple sclerosis. Tff1 expression was also localized using RNA in situ hybridization histochemistry.


RESULTS
We report for the first time on a significant transcriptional induction in cerebral Tff1 expression in both T. gondii-induced encephalitis and EAE. In contrast, Tff2 and Tff3 expression were not altered. Tff1 transcripts were predominantly localized in the internal granular layer of the cerebellum indicating neuronal expression. Furthermore, also glial cells are expected to express Tff1. Characterization of both experimental models by expression profiling (e.g., inflammasome sensors, inflammatory cytokines, microglial marker Iba1, ependymin related protein 1) revealed differences concerning the expression of the inflammasome sensor Nlrp1 and interleukin 17a.


CONCLUSIONS
The up-regulated expression of Tff1 is probably the result of a complex inflammatory process as its expression is induced by tumor necrosis factor α as well as interleukins 1β and 17. However on the transcript level, Tff1KO mice did not show any significant signs of an altered immune response after infection with T. gondii in comparison with the wild type animals.
Institute of Molecular Biology and Medicinal Chemistry, Otto-von-Guericke University Magdeburg, Germany.
Eva B
EB
Znalesniak
Ting
T
Fu
Karina
K
Guttek
Ulrike
U
Händel
Dirk
D
Reinhold
Werner
W
Hoffmann
D000818:Animals; D054022:Cerebrum / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D017403:In Situ Hybridization; D007249:Inflammation / Q000235:genetics* / Q000473:pathology*; D008297:Male; D051379:Mice; D012313:RNA / Q000235:genetics / Q000378:metabolism; D014122:Toxoplasma / Q000502:physiology; D014124:Toxoplasmosis, Animal / Q000235:genetics / Q000473:pathology; D000071163:Trefoil Factor-1 / Q000235:genetics / Q000378:metabolism*
D000071163:Trefoil Factor-1; D012313:RNA