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• W2007834915 endingPage "e111338" @default.
• W2007834915 startingPage "e111338" @default.
• W2007834915 abstract "Helicobacter pylori infection of gastric tissue results in an immune response dominated by Th1 cytokines and has also been linked with dysregulation of Sonic Hedgehog (SHH) signaling pathway in gastric tissue. However, since interactions between the cytokines and SHH during H. pylori infection are not well understood, any mechanistic understanding achieved through interpretation of the statistical analysis of experimental results in the context of currently known circuit must be carefully scrutinized. Here, we use mathematical modeling aided by restraints of experimental data to evaluate the consistency between experimental results and temporal behavior of H. pylori activated cytokine circuit model. Statistical analysis of qPCR data from uninfected and H. pylori infected wild-type and parietal cell-specific SHH knockout (PC-SHHKO) mice for day 7 and 180 indicate significant changes that suggest role of SHH in cytokine regulation. The experimentally observed changes are further investigated using a mathematical model that examines dynamic crosstalks among pro-inflammatory (IL1β, IL-12, IFNγ, MIP-2) cytokines, anti-inflammatory (IL-10) cytokines and SHH during H. pylori infection. Response analysis of the resulting model demonstrates that circuitry, as currently known, is inadequate for explaining of the experimental observations; suggesting the need for additional specific regulatory interactions. A key advantage of a computational model is the ability to propose putative circuit models for in-silico experimentation. We use this approach to propose a parsimonious model that incorporates crosstalks between NFĸB, SHH, IL-1β and IL-10, resulting in a feedback loop capable of exhibiting cyclic behavior. Separately, we show that analysis of an independent time-series GEO microarray data for IL-1β, IFNγ and IL-10 in mock and H. pylori infected mice further supports the proposed hypothesis that these cytokines may follow a cyclic trend. Predictions from the in-silico model provide useful insights for generating new hypothesis and design of subsequent experimental studies." @default.
• W2007834915 created "2016-06-24" @default.
• W2007834915 creator A5030148402 @default.
• W2007834915 creator A5054265736 @default.
• W2007834915 creator A5054677110 @default.
• W2007834915 creator A5071949521 @default.
• W2007834915 date "2014-11-03" @default.
• W2007834915 modified "2023-09-26" @default.
• W2007834915 title "Crosstalks between Cytokines and Sonic Hedgehog in Helicobacter pylori Infection: A Mathematical Model" @default.
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• W2007834915 doi "https://doi.org/10.1371/journal.pone.0111338" @default.
• W2007834915 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4218723" @default.
• W2007834915 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25364910" @default.
• W2007834915 hasPublicationYear "2014" @default.
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