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Feedbacks In Sonic Hedgehog Circuits With Cytokines In H. pylori Mediated Gastritis
Author(s) -
Marwaha Shruti,
Schumacher Michael,
Zavros Yana,
Eghbalnia Hamid
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.716.7
Subject(s) - sonic hedgehog , hedgehog signaling pathway , helicobacter pylori , proinflammatory cytokine , crosstalk , mechanism (biology) , signalling , malignancy , biology , hedgehog , immunology , gastritis , in vivo , neuroscience , inflammation , cancer research , signal transduction , microbiology and biotechnology , physics , genetics , quantum mechanics , optics
Deregulation of the Sonic Hedgehog (SHH) pathway, a critical player in normal development, has been shown to be associated with gastrointestinal abnormalities and cancers. However, the underlying mechanism remains to be fully understood. Computational models are excellent tools for investigating the complex circuitry, crosstalk, and the dynamic behavior of the associated signaling pathways. However, appropriately detailed models are lacking. Using qrt‐PCR data, algebraic methods and pathway mining, we present a model that elucidates the interactions involving SHH and cytokines activated by Helicobacter pylori , the most common pathogen associated with gastric inflammation and gastric malignancy. Focusing on the relationships between SHH and key cytokines (IL1β, IL‐12, IFNγ and IL‐10) activated by H. pylori , we describe a kinetic model that examines the dynamic regulation of these cytokines by SHH during H. pylori infection. Our mathematical model predicts that SHH, IL‐1β, NFkB and IL‐10 engage in series of feedback loops that exhibit a chronic oscillatory behavior. Predictions from our model provide useful insights for designing more targeted in vivo and in vitro experiments.