RGD Reference Report - Phosphatidylinositol 3-kinase-γ signaling promotes Campylobacter jejuni-induced colitis through neutrophil recruitment in mice. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Phosphatidylinositol 3-kinase-γ signaling promotes Campylobacter jejuni-induced colitis through neutrophil recruitment in mice.

Authors: Sun, Xiaolun  Liu, Bo  Sartor, Ryan Balfour  Jobin, Christian 
Citation: Sun X, etal., J Immunol. 2013 Jan 1;190(1):357-65. doi: 10.4049/jimmunol.1201825. Epub 2012 Nov 23.
RGD ID: 38599193
Pubmed: PMID:23180818   (View Abstract at PubMed)
PMCID: PMC3529774   (View Article at PubMed Central)
DOI: DOI:10.4049/jimmunol.1201825   (Journal Full-text)

Crypt abscesses caused by excessive neutrophil accumulation are prominent features of human campylobacteriosis and its associated pathology. The molecular and cellular events responsible for this pathological situation are currently unknown. We investigated the contribution of PI3K-γ signaling in Campylobacter jejuni-induced neutrophil accumulation and intestinal inflammation. Germ-free and specific pathogen-free Il10(-/-) and germ-free Il10(-/-);Rag2(-/-) mice were infected with C. jejuni (10(9) CFU/mouse). PI3K-γ signaling was manipulated using either the pharmacological PI3K-γ inhibitor AS252424 (i.p. 10 mg/kg daily) or genetically using Pi3k-γ(-/-) mice. After up to 14 d, inflammation was assessed histologically and by measuring levels of colonic Il1β, Cxcl2, and Il17a mRNA. Neutrophils were depleted using anti-Gr1 Ab (i.p. 0.5 mg/mouse/every 3 d). Using germ-free Il10(-/-);Rag2(-/-) mice, we observed that innate immune cells are the main cellular compartment responsible for campylobacteriosis. Pharmacological blockade of PI3K-γ signaling diminished C. jejuni-induced intestinal inflammation, neutrophil accumulation, and NF-κB activity, which correlated with reduced Il1β (77%), Cxcl2 (73%), and Il17a (72%) mRNA accumulation. Moreover, Pi3k-γ(-/-) mice pretreated with anti-IL-10R were resistant to C. jejuni-induced intestinal inflammation compared with Wt mice. This improvement was accompanied by a reduction of C. jejuni translocation into the colon and extraintestinal tissues and by attenuation of neutrophil migratory capacity. Furthermore, neutrophil depletion attenuated C. jejuni-induced crypt abscesses and intestinal inflammation. Our findings indicate that C. jejuni-induced PI3K-γ signaling mediates neutrophil recruitment and intestinal inflammation in Il10(-/-) mice. Selective pharmacological inhibition of PI3K-γ may represent a novel means to alleviate severe cases of campylobacteriosis, especially in antibiotic-resistant strains.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PIK3CGHumancampylobacteriosis treatmentISOPik3cg (Mus musculus) RGD 
Pik3cgRatcampylobacteriosis treatmentISOPik3cg (Mus musculus) RGD 
Pik3cgMousecampylobacteriosis treatmentIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pik3cg  (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma)

Genes (Mus musculus)
Pik3cg  (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma)

Genes (Homo sapiens)
PIK3CG  (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma)


Additional Information