title: Differential responses of normal human coronary artery endothelial cells against multiple cytokines comparatively assessed by gene expression profiles.
abstract: Endothelial cells play an important role in terms of biological functions by responding to a variety of stimuli in the blood. However, little is known about the molecular mechanism involved in rendering the variety in the cellular response. To investigate the variety of the cellular responses against exogenous stimuli at the gene expression level, we attempted to describe the cellular responses with comprehensive gene expression profiles, dissect them into multiple response patterns, and characterize the response patterns according to the information accumulated so far on the genes included in the patterns. We comparatively analyzed in parallel the gene expression profiles obtained with DNA microarrays from normal human coronary artery endothelial cells (HCAECs) stimulated with multiple cytokines, interleukin-1beta, tumor necrosis factor-alpha, interferon-beta, interferon-gamma, and oncostatin M, which are profoundly involved in various functional responses of endothelial cells. These analyses revealed that the cellular responses of HCAECs against these cytokines included at least 15 response patterns specific to a single cytokine or common to multiple cytokines. Moreover, we statistically extracted genes contained within the individual response patterns and characterized the response patterns with the genes referring to the previously accumulated findings including the biological process defined by the Gene Ontology Consortium (GO). Out of the 15 response patterns in which at least one gene was successfully extracted through the statistical approach, 11 response patterns were differentially characterized by representing the number of genes contained in individual criteria of the biological process in the GO only. The approach to dissect cellular responses into response patterns and to characterize the pattern at the gene expression level may contribute to the gaining of insight for untangling the diversity of cellular functions.
authors.affiliation: Graduate School of Life and Environmental Science, University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Miura
authors.forename: Reiko
authors.initials: R
authors.lastname: Honma
authors.forename: Takushi
authors.initials: T
authors.lastname: Togashi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yanagisawa
authors.forename: Emi
authors.initials: E
authors.lastname: Ito
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Imai
authors.forename: Takao
authors.initials: T
authors.lastname: Isogai
authors.forename: Naoki
authors.initials: N
authors.lastname: Goshima
authors.forename: Shinya
authors.initials: S
authors.lastname: Watanabe
authors.forename: Nobuo
authors.initials: N
authors.lastname: Nomura
mesh_terms: D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D003106:Colon / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans
chemical_list: D016207:Cytokines