Phagocytosis of N-acetyl-D-glucosamine particles, a Th1 adjuvant, by RAW 264.7 cells results in MAPK activation and TNF-alpha, but not IL-10, production.
A practical and highly effective Th1 adjuvant should induce Th1 cytokines (IL-12, IL-18, and TNF-alpha) but not the Th2 cytokine IL-10, an inhibitor of Th1 responses. In this study, phagocytosis of N-acetyl-d-glucosamine polymer (chitin) particles by RAW 264.7 cells, a murine macrophage-like cell line, resulted in phosphorylation of MAPK (p38, Erk 1/2, and JNK), and production of relatively high levels of TNF-alpha and COX-2 with increased PGE(2) release. Similar results were observed in response to oligonucleotides with CpG motifs, mycobacterial components and endotoxin. However, these bacterial components also induced a large amount of IL-10. Chitin particles, in contrast, failed to induce detectable levels of IL-10, although the production of high levels of PGE(2) and TNF-alpha and the activation of MAPK's are potentially positive signals for IL-10 production. Thus, our results indicate that chitin particles act as a unique Th1 adjuvant for macrophages without inducing increased production of IL-10.
Nishiyama
Akihito
A
Department of Biomedical Sciences, Florida Atlantic University, Boca Raton, FL 33431-0991, USA. nishiyam@fau.edu
Tsuji
Shoutaro
S
Yamashita
Makiko
M
Henriksen
Ruth Ann
RA
Myrvik
Quentin N
QN
Shibata
Yoshimi
Y
D000117:Acetylglucosamine / Q000378:metabolism*; D000276:Adjuvants, Immunologic / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D002460:Cell Line; D002686:Chitin / Q000378:metabolism; D004789:Enzyme Activation / Q000276:immunology; D005260:Female; D016753:Interleukin-10 / Q000096:biosynthesis; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010316:Particle Size; D010587:Phagocytosis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000276:Adjuvants, Immunologic; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002686:Chitin; D020928:Mitogen-Activated Protein Kinases; D000117:Acetylglucosamine