Gliadin peptides activate blood monocytes from patients with celiac disease.
To elucidate the role of innate immune responses in celiac disease, we investigated the effect of gliadin on blood monocytes from patients with celiac disease. Gliadin induced substantial TNF-alpha and IL-8 production by monocytes from patients with active celiac disease, lower levels by monocytes from patients with inactive celiac disease, and even lower levels by monocytes from healthy donors. In healthy donor monocytes gliadin induced IL-8 from monocytes expressing HLA-DQ2 and increased monocyte expression of the costimulatory molecules CD80 and CD86, the dendritic cell marker CD83, and the activation marker CD40. Gliadin also increased DNA binding activity of NF-kappaB p50 and p65 subunits in monocytes from celiac patients, and NF-kappaB inhibitors reduced both DNA binding activity and cytokine production. Thus, gliadin activation of HLA-DQ2(+) monocytes leading to chemokine and proinflammatory cytokine production may contribute to the host innate immune response in celiac disease.
Cinova
Jana
J
Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Palová-Jelínková
Lenka
L
Smythies
Lesley E
LE
Cerná
Marie
M
Pecharová
Barbara
B
Dvorák
Milos
M
Fruhauf
Pavel
P
Tlaskalová-Hogenová
Helena
H
Smith
Phillip D
PD
Tucková
Ludmila
L
D015703:Antigens, CD / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002446:Celiac Disease / Q000276:immunology* / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis*; D005434:Flow Cytometry; D005903:Gliadin / Q000378:metabolism*; D006683:HLA-DQ Antigens / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis; D008262:Macrophage Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000097802:CD83 Antigen
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D016207:Cytokines; D005903:Gliadin; D006683:HLA-DQ Antigens; D007136:Immunoglobulins; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D000097802:CD83 Antigen; C053186:HLA-DQ2 antigen