Interleukin-11 regulation of gene expression and signal transduction in 3T3-L1 adipocytes / by Raleigh E. Tenney.
| Author/creator | Tenney, Raleigh E. author. |
| Other author | Kalmus, Gerhard W., degree supervisor. |
| Other author | East Carolina University. Department of Biology. |
| Format | Theses and dissertations |
| Production | 2003. |
| Description | ix, 71 leaves : illustrations (some color) ; 28 cm |
| Supplemental Content | Access via ScholarShip |
| Subjects |
| Summary | The purpose of this study was to identify alterations in gene expression and signal transduction pathways regulated by IL-I1 treatment of 3T3-L1 adipocytes. As a consequence of obesity, pro-inflammatory cytokines synthesized and secreted by adipocytes have negative effects on metabolism, resulting in insulin resistance and hyperglycemia, which contribute to the development of diabetes. IL-I1 is an anti-inflammatory cytokine that works to counteract pro-inflammatory responses. With these considerations we examined IL-I1 treated adipocytes using gene expression microarray analysis and western analysis for alteration in the expression of genes and proteins that would have an effect on adipocyte metabolism, potentially diabetes. Microarray analysis demonstrated that many changes occur in gene expression with IL-I1 treatment of adipocytes. Most strikingly was an increase in expression of G[alpha]i2 and a reciprocal decrease in G[alpha]s gene expression. G proteins function as intracellular second messengers and G[alpha]i2 has been demonstrated to be essential for insulin sensitivity in adipocytes. While microarray analysis provided data indicating significant changes in gene expression with IL-I1 treatment, RT-PCR analysis demonstrated that while expression of the genes was altered, the magnitude was markedly less than indicated by microarray analysis determined. Western analysis demonstrated that G[alpha]i2 protein content was also increased. Additionally the protein content of several critical transcription factors was also demonstrated to change, with increases in PPAR[gamma] and C/EBP[delta], whereas C/EBP[alpha] and CHOP-10 were decreased after treatment with IL-I1. The p44/42 MAP kinase and PI3 kinase signal transduction pathways were activated by IL-I1 in the adipocytes. Results showed activation of p70 S6 kinase was mediated by the PI3 kinase pathway and to a lesser extent by the MAP kinase pathway. Phosphorylation of STAT1 and STAT3 was also observed, but phosphorylation of a specific JAK could not be defined. Activation of transcription factors CREB and ATF1 were demonstrated to be mediated through MAP kinase signaling. |
| General note | Presented to the faculty of the Department of Biology. |
| General note | Advisor: Gerhard W. Kalmus |
| Dissertation note | M.S. East Carolina University 2003 |
| Bibliography note | Includes bibliographical references (leaves 61-67). |
| Genre/form | Academic theses. |
| Genre/form | Academic theses. |
| Genre/form | Thèses et écrits académiques. |
Availability
| Library | Location | Call Number | Status | Item Actions |
|---|---|---|---|---|
| Joyner | University Archives | ASK AT SPECIAL COLLECTIONS DESK | ✔ Available | Request Material |
| Electronic Resources | Access Content Online | ✔ Available |