Differential effects of retinoids on pokeweed mitogen induced B-cell proliferation vs immunoglobulin synthesis.
The effects of three retinoids, all-trans-retinoic acid (RA), 13-cis-retinoic acid (cRA), and N-(4-hydroxyphenyl) retinamide (4-HPR) on mouse splenocyte responses to pokeweed mitogen (PWM) and Escherichia coli lipopolysaccharide (LPS) in vitro were evaluated. All three retinoids caused a dose dependent increase in the proliferative response to PWM. The retinoids hierarchy of efficacy based on potentiation of PWM-induced splenocyte proliferation was RA greater than cRA greater than 4-HPR. 13-cis-retinoic acid and 4-HPR also resulted in significant increases in Ig secretion in response to PWM. However, RA did not produce a significant increase in secretion compared with cells treated with PWM alone. The efficacy hierarchy of retinoids ability to potentiate Ig secretion was 4-HPR greater than cRA greater than RA. All three compounds did not affect Ig secretion from LPS-stimulated splenocytes and produced dose dependent decreases in proliferation. Both inhibition of LPS-induced proliferation and potentiation of PWM-induced proliferation were maximal when the retinoids were added during the first hour of culture. These results indicate that retinoids have a differential effect on Ig secretion and B-cell proliferation based on structural differences of the retinoids. Potentiation of proliferation and Ig secretion are both T-cell dependent and could be a result of increased lymphokine synthesis by the T-cells or increased responsiveness to the effects of the T-cell produced lymphokines.
Dillehay
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DL
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322.
Jiang
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XL
Lamon
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EW
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D005260:Female; D017313:Fenretinide; D007136:Immunoglobulins / Q000096:biosynthesis*; D066298:In Vitro Techniques; D015474:Isotretinoin / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D011043:Pokeweed Mitogens / Q000276:immunology; D012176:Retinoids / Q000494:pharmacology*; D014212:Tretinoin / Q000031:analogs & derivatives / Q000494:pharmacology
D007136:Immunoglobulins; D011043:Pokeweed Mitogens; D012176:Retinoids; D017313:Fenretinide; D014212:Tretinoin; D015474:Isotretinoin