Effects of estrogen receptor agonists on regulation of the inflammatory response in astrocytes from young adult and middle-aged female rats.
Estrogen has been shown to attenuate the inflammatory response following injury or lipopolysaccharide treatment in several organ systems. Estrogen's actions are transduced through two estrogen receptor sub-types, estrogen receptor (ER) -alpha and estrogen receptor-beta, whose actions may be overlapping or independent of each other. The present study examined the effects of ERalpha- and ERbeta-specific ligands in regulating the inflammatory response in primary astrocyte cultures. Pre-treatment with 17beta-estradiol (ERalpha/ERbeta agonist), HPTE (ERalpha agonist/ERbeta antagonist) and DPN (ERbeta agonist) led to attenuation of IL-1beta, TNFalpha, and MMP-9 in astrocyte media derived from young adult (3-4 mos.) and reproductive senescent female (9-11 mos., acyclic) astrocyte cultures, while pretreatment with PPT (ERalpha agonist) attenuated IL-1beta (but not MMP-9) in both young and senescent-derived astrocyte cultures. Our previous work determined that 17beta-estradiol was unable to attenuate the LPS-induced increase in IL-1beta in olfactory bulb primary microglial cultures derived from either young adult or reproductive senescent females. In young adult-derived microglial cultures, the LPS-induced increase in IL-1beta was not attenuated by pre-treatment with 17beta-estradiol, PPT or HPTE. Interestingly, the ERbeta agonist, DPN significantly decreased IL-1beta following LPS treatment in young adult-derived microglia. Thus while both microglia and astrocytes synthesize and release inflammatory mediators, the present data shows that compounds which bind ERbeta are more effective in attenuating proinflammatory cytokines in both cell types and may therefore be a more effective agent for future therapeutic use.
Lewis
Danielle K
DK
Department of Neuroscience and Experimental Therapeutics, TAMU Health Science Center, College Station, TX 77843-1114, USA.
Johnson
Adam B
AB
Stohlgren
Shannon
S
Harms
Ashley
A
Sohrabji
Farida
F
D000375:Aging; D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D039481:CD11b Antigen / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004347:Drug Interactions; D004967:Estrogens / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016202:N-Methylaspartate / Q000633:toxicity; D009830:Olfactory Bulb / Q000166:cytology; D010052:Ovariectomy / Q000379:methods; D051381:Rats; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C100745:Aif1 protein, rat; D039481:CD11b Antigen; D002135:Calcium-Binding Proteins; D004967:Estrogens; D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; C489787:MAP2 protein, rat; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D011960:Receptors, Estrogen; D014409:Tumor Necrosis Factor-alpha; D016202:N-Methylaspartate