TY - JOUR
T1 - Activated platelets enhance IL-10 secretion and reduce TNF-α secretion by monocytes
AU - Gudbrandsdottir, Sif
AU - Hasselbalch, Hans C.
AU - Nielsen, Claus H.
PY - 2013/10/15
Y1 - 2013/10/15
N2 - Activated platelets are known to modulate immune responses by secreting or shedding a range of immunomodulatory substances. We examined the influence of activated platelets on cytokine production by normal human mononuclear cells, induced by tetanus toxoid (TT), human thyroglobulin (TG),Escherichia coliLPS, or intactPorphyromonas gingivalis. Addition of platelets activated by thrombin-receptor-Activating peptide enhanced IL-10 production induced by LPS (p< 0.001), TG (p< 0.05), andP. gingivalis (p< 0.01), and reduced the production of TNF-αinduced by LPS (p< 0.001), TG (p< 0.05), andP. gingivalis(p< 0.001), and of IL-6 in LPS- andP. gingivalis-stimulated cultures (p< 0.001). Similar effects on IL-10 and TNF-αproduction were observed on addition of platelet supernatant to mononuclear cells, whereas addition of recombinant soluble CD40L mimicked the effects on IL-10 production. Moreover, Ab-mediated blockade of CD40L counteracted the effect of platelets and platelet supernatants on TNF-αproduction. Monocytes separated into two populations with respect to IL-10 production induced by TG; the high-secreting fraction increased from 0.8 to 2.1% (p< 0.001) on addition of activated platelets. Adherence of platelets increased TG- and TTinduced IL-10 secretion by monocytes (p< 0.05). In addition, activated platelets inhibited CD4 + T cell proliferation elicited by TT (p< 0.001) andP. gingivalis(p< 0.001). Our findings suggest that activated platelets have anti-inflammatory properties related to the interaction between CD40L and CD40, and exert a hitherto undescribed immunoregulatory action by enhancing IL-10 production and inhibiting TNF-αproduction by monocytes.
AB - Activated platelets are known to modulate immune responses by secreting or shedding a range of immunomodulatory substances. We examined the influence of activated platelets on cytokine production by normal human mononuclear cells, induced by tetanus toxoid (TT), human thyroglobulin (TG),Escherichia coliLPS, or intactPorphyromonas gingivalis. Addition of platelets activated by thrombin-receptor-Activating peptide enhanced IL-10 production induced by LPS (p< 0.001), TG (p< 0.05), andP. gingivalis (p< 0.01), and reduced the production of TNF-αinduced by LPS (p< 0.001), TG (p< 0.05), andP. gingivalis(p< 0.001), and of IL-6 in LPS- andP. gingivalis-stimulated cultures (p< 0.001). Similar effects on IL-10 and TNF-αproduction were observed on addition of platelet supernatant to mononuclear cells, whereas addition of recombinant soluble CD40L mimicked the effects on IL-10 production. Moreover, Ab-mediated blockade of CD40L counteracted the effect of platelets and platelet supernatants on TNF-αproduction. Monocytes separated into two populations with respect to IL-10 production induced by TG; the high-secreting fraction increased from 0.8 to 2.1% (p< 0.001) on addition of activated platelets. Adherence of platelets increased TG- and TTinduced IL-10 secretion by monocytes (p< 0.05). In addition, activated platelets inhibited CD4 + T cell proliferation elicited by TT (p< 0.001) andP. gingivalis(p< 0.001). Our findings suggest that activated platelets have anti-inflammatory properties related to the interaction between CD40L and CD40, and exert a hitherto undescribed immunoregulatory action by enhancing IL-10 production and inhibiting TNF-αproduction by monocytes.
UR - http://www.scopus.com/inward/record.url?scp=84885460302&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1201103
DO - 10.4049/jimmunol.1201103
M3 - Article
C2 - 24048901
AN - SCOPUS:84885460302
SN - 0022-1767
VL - 191
SP - 4059
EP - 4067
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -