title: Substance P in polymicrobial sepsis: molecular fingerprint of lung injury in preprotachykinin-A-/- mice.
abstract: Deletion of mouse preprotachykinin-A (PPTA), which encodes mainly for neuropeptide substance P, has been shown to protect against lung injury and mortality in sepsis. This study explored microarray-based differential gene expression profiles in mouse lung tissue 8 h after inducing microbial sepsis and the effect of PPTA gene deletion. A range of genes differentially expressed (more than two-fold) in microarray analysis was assessed, comparing wild-type and PPTA-knockout septic mice with their respective sham controls, and the data were further validated. Genetic deletion of substance P resulted in a significantly different expression profile of genes involved in inflammation and immunomodulation after the induction of sepsis, compared with wild-type mice. Interestingly, apart from the various proinflammatory mediators, the antiinflammatory cytokine interleukin-1 receptor antagonist gene (IL1RN) was also elevated much more in PPTA(-/-) septic mice. In addition, semiquantitative RT-PCR analysis supported the microarray data. The microarray data imply that the elevated levels of inflammatory gene expression in the early stages of sepsis in PPTA-knockout mice are possibly aimed to resolve the infection without excessive immunosuppression. As scientists are divided over the effects of pro- and antiinflammatory mediators in sepsis, it seems prudent to define the status depending on a complete genome profile. This is the first report exploring pulmonary gene expression profiles using microarray analysis in PPTA-knockout mice subjected to cecal ligation and puncture-induced sepsis and providing additional biological insight into the protection received against lung injury and mortality.
authors.affiliation: Cardiovascular Biology Program, Department of Pharmacology, Yong Loo Lin School of Medicine,National University of Singapore, Singapore.
authors.forename: Akhil
authors.initials: A
authors.lastname: Hegde
authors.forename: Ramasamy
authors.initials: R
authors.lastname: Tamizhselvi
authors.forename: Jayapal
authors.initials: J
authors.lastname: Manikandan
authors.forename: Alirio J
authors.initials: AJ
authors.lastname: Melendez
authors.forename: Shabbir M
authors.initials: SM
authors.lastname: Moochhala
authors.forename: Madhav
authors.initials: M
authors.lastname: Bhatia
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016470:Bacteremia / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics / Q000378:metabolism; D008171:Lung Diseases / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D011498:Protein Precursors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015320:Tachykinins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: D018925:Chemokines; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D011498:Protein Precursors; D015320:Tachykinins; C044206:preprotachykinin
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