Is there an interaction between interleukin-10 and interleukin-22?
Interleukin(IL)-10 and IL-22 are structurally related cytokines. Their heterodimeric receptors consist of the cytokine-specific chains IL-10R1 and IL-22R1, respectively, and the common chain IL-10R2. This study focused on the question of whether IL-10 modulates IL-22 effects and vice versa. This question is important because IL-10 and IL-22 exert anti- and proinflammatory effects, respectively, and, as we show here, are simultaneously present in both systemic and local inflammation. The revealed lacking concomitance of IL-10R1 and IL-22R1 on identical cells excluded any possible interaction between IL-10 and IL-22 apart from the competition for IL-10R2. To study this competition, monocytes and hepatocytes were chosen. The dependence of the cytokine action on IL-10R2 was verified. Interestingly, no influence of IL-22 on IL-10 effects was observed. The same was true when IL-22 was used in complex with IL-22-binding protein. Similarly, no influence of IL-10 was found on IL-22 action. This missing competition seemed to be due to a lack of binding between IL-10R2 and the native cytokines in the absence of their corresponding R1 chain. However, IL-10R2 interacted with defined IL-10- and IL-22-derived peptides supporting the hypothesis that cytokine binding to its corresponding R1 chain creates a binding site on this cytokine for IL-10R2.
Wolk
K
K
Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, D-10117 Berlin, Germany.
Witte
E
E
Reineke
U
U
Witte
K
K
Friedrich
M
M
Sterry
W
W
Asadullah
K
K
Volk
H-D
HD
Sabat
R
R
D000818:Animals; D004347:Drug Interactions; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism* / Q000494:pharmacology; D007378:Interleukins / Q000378:metabolism* / Q000494:pharmacology; D019169:Jurkat Cells; D020014:K562 Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D011485:Protein Binding; D018123:Receptors, Interleukin / Q000378:metabolism*; D053701:Receptors, Interleukin-10; D000097043:Interleukin-22
D016753:Interleukin-10; D007378:Interleukins; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D000097043:Interleukin-22; C415369:interleukin-22 receptor