Age-dependent responses of glial cells and leptomeninges during systemic inflammation.
Systemic inflammation causes the age-dependent differential glial responses, but little is known about how age influences the barrier function of leptomeninges during systemic inflammation. This study was conducted to elucidate the relationship between the glial responses and the levels of tight junction proteins, occludin and ZO-1, in adjuvant arthritis (AA) rats. In young AA rats, microglia and astrocytes localized to the proximity of the leptomeninges expressed interleukin (IL)-10 and transforming growth factor (TGF)-beta1. The level of occludin significantly increased. In middle-aged AA rats, however, glial cells expressed IL-1beta and prostaglandin E(2) (PGE(2))-synthesizing enzymes. Furthermore, occludin and ZO-1 significantly decreased, resulting in the increased permeability of leptomeninges. In the cultured leptomeningeal cells, IL-1beta and PGE(2) caused a marked loss of occludin and ZO-1, respectively. Pretreatment with IL-10 and TGF-beta1 significantly antagonized their effects. These findings establish that age strongly influences the barrier functions of the leptomeninges through the age-dependent differential glial responses during systemic inflammation.
Laboratory of Oral Aging Science, Faculty of Dental Sciences, Kyushu University, Fukuoka 812-8582, Japan. zhouw@dent.kyushu-u.ac.jp
Zhou
Z
Wu
Yukie
Y
Tokuda
Xin-Wen
XW
Zhang
Hiroshi
H
Nakanishi
D000375:Aging; D000818:Animals; D001169:Arthritis, Experimental / Q000503:physiopathology*; D001253:Astrocytes / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000503:physiopathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D007249:Inflammation / Q000503:physiopathology*; D016753:Interleukin-10 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008578:Meninges / Q000503:physiopathology*; D009457:Neuroglia / Q000502:physiology*; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D010750:Phosphoproteins; C569044:Tjp1 protein, rat; D053773:Transforming Growth Factor beta1; D062826:Zonula Occludens-1 Protein; D016753:Interleukin-10; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C489691:Ptgs2 protein, rat; D000071876:Prostaglandin-E Synthases; C497818:Ptges protein, rat; D015232:Dinoprostone