1Alpha,25-dihydroxyvitamin D3 inhibits CD40L-induced pro-inflammatory and immunomodulatory activity in human monocytes.
CD40 ligand (CD40L) stimulation induces proinflammatory and immunomodulatory activity in monocytes. Here, we report on the effects of the steroid hormone 1alpha,25-dihydroxyvitamin D3 (1,25D3) on human blood monocytes that have been stimulated with the CD40L ligand. Co-treatment of CD40L-stimulated monocytes with 1,25D3 resulted in reduced production and secretion of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, as well as in reduced expression of the surface co-stimulatory molecules CD80 and CD86. In addition, costimulation of CD4+ T lymphocytes by monocytes co-treated with CD40L and 1,25D3 resulted in reduced cell proliferation and diminished interferon (IFN)-gamma but enhanced IL-10 production by CD4+ T cells. Finally, 1,25D3 interfered with the ability of CD40L to rescue monocytes from apoptosis induced by serum withdrawal. These findings suggest that 1,25D3 may regulate the interaction of monocytes with T cells or other cell types that express CD40L, thus influencing the outcome of the immune or inflammatory response.
Almerighi
Cristiana
C
Department of Internal Medicine, University of Rome Tor Vergata, via Montpellier 1, 00133 Rome, Italy.
Sinistro
Anna
A
Cavazza
Antonella
A
Ciaprini
Chiara
C
Rocchi
Giovanni
G
Bergamini
Alberto
A
D023201:CD40 Ligand / Q000276:immunology*; D002117:Calcitriol / Q000494:pharmacology*; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology*
D007155:Immunologic Factors; D023201:CD40 Ligand; D002117:Calcitriol