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Estrogen increases CD40 ligand expression in T cells from women with systemic lupus erythematosus.
J Rheumatol 2001; 28(12):2644-9JR

Abstract

OBJECTIVE

To examine the in vitro effects of estrogen on CD40 ligand (CD40L) expression in peripheral blood T cells isolated from patients with systemic lupus erythematosus (SLE) and normal controls.

METHODS

T cells from female patients with SLE and controls were cultured in serum-free medium without and with 2-fluoroestradiol. Some T cells were activated by further culture on anti-CD3 coated plates. Calcineurin was activated in some T cells by culture in ionomycin. Cell surface CD40L was quantitated by FACS analysis. mRNA expression was measured using semiquantitative PCR.

RESULTS

Lupus T cells cultured in medium containing 2-fluoroestradiol showed a significant (p = 0.04) increase in the amount of CD40L on the cell surface, but not in the number of positive cells, compared to the same T cells cultured without estradiol. Estradiol did not significantly change CD40L expression on the surface of T cells from normal women. In addition, the difference in cell surface CD40L between T cells cultured without and with estradiol was significantly greater (p = 0.048) on SLE than on normal T cells. Culture of SLE T cells in medium containing 2-fluoroestradiol followed by T cell receptor (TCR) activation for 2 h using anti-CD3 resulted in a significant (p = 0.04) estrogen dependent increase in CD40L mRNA. The estrogen dependent increases in SLE T cell CD40L mRNA and cell surface protein were blocked by the estrogen receptor antagonist ICI 182,780. SLE and normal T cells pretreated with estradiol and cultured with ionomycin for 2 h to activate calcineurin showed no significant differences in CD40L mRNA.

CONCLUSION

These results suggest that estradiol, working through the estrogen receptor, stimulates the expression of CD40L in unstimulated and activated SLE T cells. Estradiol effects may be exerted on multiple regulatory steps that control CD40L expression. The estrogen dependent increase in CD40L expression could hyperstimulate SLE T cells and thereby contribute to the pathogenesis of SLE.

Authors+Show Affiliations

School of Biological Sciences, University of Missouri-Kansas City, USA. VRider@pittstate.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11764210

Citation

Rider, V, et al. "Estrogen Increases CD40 Ligand Expression in T Cells From Women With Systemic Lupus Erythematosus." The Journal of Rheumatology, vol. 28, no. 12, 2001, pp. 2644-9.
Rider V, Jones S, Evans M, et al. Estrogen increases CD40 ligand expression in T cells from women with systemic lupus erythematosus. J Rheumatol. 2001;28(12):2644-9.
Rider, V., Jones, S., Evans, M., Bassiri, H., Afsar, Z., & Abdou, N. I. (2001). Estrogen increases CD40 ligand expression in T cells from women with systemic lupus erythematosus. The Journal of Rheumatology, 28(12), pp. 2644-9.
Rider V, et al. Estrogen Increases CD40 Ligand Expression in T Cells From Women With Systemic Lupus Erythematosus. J Rheumatol. 2001;28(12):2644-9. PubMed PMID: 11764210.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Estrogen increases CD40 ligand expression in T cells from women with systemic lupus erythematosus. AU - Rider,V, AU - Jones,S, AU - Evans,M, AU - Bassiri,H, AU - Afsar,Z, AU - Abdou,N I, PY - 2002/1/5/pubmed PY - 2002/5/3/medline PY - 2002/1/5/entrez SP - 2644 EP - 9 JF - The Journal of rheumatology JO - J. Rheumatol. VL - 28 IS - 12 N2 - OBJECTIVE: To examine the in vitro effects of estrogen on CD40 ligand (CD40L) expression in peripheral blood T cells isolated from patients with systemic lupus erythematosus (SLE) and normal controls. METHODS: T cells from female patients with SLE and controls were cultured in serum-free medium without and with 2-fluoroestradiol. Some T cells were activated by further culture on anti-CD3 coated plates. Calcineurin was activated in some T cells by culture in ionomycin. Cell surface CD40L was quantitated by FACS analysis. mRNA expression was measured using semiquantitative PCR. RESULTS: Lupus T cells cultured in medium containing 2-fluoroestradiol showed a significant (p = 0.04) increase in the amount of CD40L on the cell surface, but not in the number of positive cells, compared to the same T cells cultured without estradiol. Estradiol did not significantly change CD40L expression on the surface of T cells from normal women. In addition, the difference in cell surface CD40L between T cells cultured without and with estradiol was significantly greater (p = 0.048) on SLE than on normal T cells. Culture of SLE T cells in medium containing 2-fluoroestradiol followed by T cell receptor (TCR) activation for 2 h using anti-CD3 resulted in a significant (p = 0.04) estrogen dependent increase in CD40L mRNA. The estrogen dependent increases in SLE T cell CD40L mRNA and cell surface protein were blocked by the estrogen receptor antagonist ICI 182,780. SLE and normal T cells pretreated with estradiol and cultured with ionomycin for 2 h to activate calcineurin showed no significant differences in CD40L mRNA. CONCLUSION: These results suggest that estradiol, working through the estrogen receptor, stimulates the expression of CD40L in unstimulated and activated SLE T cells. Estradiol effects may be exerted on multiple regulatory steps that control CD40L expression. The estrogen dependent increase in CD40L expression could hyperstimulate SLE T cells and thereby contribute to the pathogenesis of SLE. SN - 0315-162X UR - https://www.unboundmedicine.com/medline/citation/11764210/Estrogen_increases_CD40_ligand_expression_in_T_cells_from_women_with_systemic_lupus_erythematosus_ L2 - http://www.jrheum.org/cgi/pmidlookup?view=long&pmid=11764210 DB - PRIME DP - Unbound Medicine ER -