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Exploration of a mammary epithelial cell model for the study of inflammation and mechanisms of anti-inflammatory activity in medicinal plants

Al-Maalouf, Samar Wadih
http://rave.ohiolink.edu/etdc/view?acc_num=osu1166806742

Abstract Details

2007, Doctor of Philosophy, Ohio State University, Animal Science.
Failure to terminate the inflammatory response results in chronic inflammation that may lead to disease or cancer, especially in epithelial cells. We explored mammary epithelial cells as a model to identify mechanisms of anti-inflammatory activity in epithelia alone in the absence of immune cells. Bacterial endotoxin (ET) added to SCp2 mammary secretory epithelial cells: (1) induced both interleukin-6 (IL-6) secretion and nitric oxide (NO) production, but with unexpected delay in expression of mRNA for iNOS compared to IL-6; and (2) NFκB activation by 1 h after ET application (post-ET) that was transient for NFκB/p65 but persisted for NFκB/p50. Selective inhibition of NFκB activation by Wedelolactone reduced ET-induced expression of IL-6 mRNA and protein but not iNOS mRNA or NO production, suggesting differences in ET-induced IL-6 and iNOS regulation via NFκB activation. Serum supplementation but not soluble extracellular matrix (EHS) enhanced ET-induced IL-6 mRNA expression and protein secretion without affecting iNOS mRNA expression or NO production, confirming the different modes of regulation of IL-6 and iNOS expressions. Culturing SCp2 cells on a confluent monolayer of SCg6 mouse mammary myoepithelial cells increased IL-6 secretion dramatically even in the absence of ET, with ET treatment further increasing IL-6 secretion but having little effect on induction of NO production over that for SCp2 cells alone; showing importance of microenvironment and cell-cell interaction in regulation of inflammation and likely its link to cancer in epithelia. ET-induced inflammation in SCp2 cells was used to screen and identify anti-inflammatory fractions of methanol extracts of wild Lebanese Centaurea ainetensis, used in Lebanese folk medicine to treat inflammatory diseases. A partially purified solid phase (SPE columns) methanolic elution fraction of C. ainetensis followed by methanol gradient elution on reverse phase HPLC chromatography (RP-HPLC) strongly inhibited ET-induced IL-6 secretion with little cytotoxicity. The partially purified fraction of C. ainetensis also reduced ET-induced NO production by SCp2 cells, and inhibited the ET-induced expression of mRNA for iNOS without affecting IL-6 mRNA expression, suggesting inhibition of alternative pathways in addition to NFκB for regulation of inflammation.
Floyd Schanbacher (Advisor)
Charles Brooks (Other)
James DeWille (Other)
Joy Pate (Other)
227 p.
Inflammation; Endotoxin; LPS; Mammary epithelial cells; NFkB; IL-6; nitric oxide; NO; iNOS; IKK; cell-cell interaction; ECM; extracellular matrix; medicinal plant; Centaurea ainetensis; Wedelolactone

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Citations

  • Al-Maalouf, S. W. (2007). Exploration of a mammary epithelial cell model for the study of inflammation and mechanisms of anti-inflammatory activity in medicinal plants [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1166806742

    APA Style (7th edition)

  • Al-Maalouf, Samar. Exploration of a mammary epithelial cell model for the study of inflammation and mechanisms of anti-inflammatory activity in medicinal plants. 2007. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1166806742.

    MLA Style (8th edition)

  • Al-Maalouf, Samar. "Exploration of a mammary epithelial cell model for the study of inflammation and mechanisms of anti-inflammatory activity in medicinal plants." Doctoral dissertation, Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=osu1166806742

    Chicago Manual of Style (17th edition)

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This open access ETD is published by The Ohio State University and OhioLINK.