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Cyclooxygenase Inhibitors, Aspirin and Ibuprofen, Inhibit MHC-restricted Antigen Presentation in Dendritic Cells.

Kim HJ, Lee YH, Im SA, Kim K, Lee CK - Immune Netw (2010)

Bottom Line: In addition, the DCs generated in the presence of low concentrations of the drugs exhibit a profoundly suppressed capability to present MHC-restricted antigens.Aspirin and ibuprofen did not inhibit the phagocytic activity of DCs, the expression level of total MHC molecules and co-stimulatory molecules on DCs.These results demonstrate that aspirin and ibuprofen inhibit the intracellular processing event of the phagocytosed antigen, and further suggest that prolonged administration of NSAIDs in high doses may impair the capability of DCs to present antigens in asiociation with MHC molecules.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea.

ABSTRACT

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve pain, reduce fever and inhibit inflammation. NSAIDs function mainly through inhibition of cyclooxygenase (COX). Growing evidence suggests that NSAIDs also have immunomodulatory effects on T and B cells. Here we examined the effects of NSAIDs on the antigen presenting function of dendritic cells (DCs).

Methods: DCs were cultured in the presence of aspirin or ibuprofen, and then allowed to phagocytose biodegradable microspheres containing ovalbumin (OVA). After washing and fixing, the efficacy of OVA peptide presentation by DCs was evaluated using OVA-specific CD8 and CD4 T cells.

Results: Aspirin and ibuprofen at high concentrations inhibited both MHC class I and class II-restricted presentation of OVA in DCs. In addition, the DCs generated in the presence of low concentrations of the drugs exhibit a profoundly suppressed capability to present MHC-restricted antigens. Aspirin and ibuprofen did not inhibit the phagocytic activity of DCs, the expression level of total MHC molecules and co-stimulatory molecules on DCs. Ibuprofen rather increased the expression level of total MHC molecules and co-stimulatory molecules on DCs.

Conclusion: These results demonstrate that aspirin and ibuprofen inhibit the intracellular processing event of the phagocytosed antigen, and further suggest that prolonged administration of NSAIDs in high doses may impair the capability of DCs to present antigens in asiociation with MHC molecules.

No MeSH data available.


Related in: MedlinePlus

Effects of aspirin and ibuprofen on the expression of MHC molecules. DC2.4 cells were cultured with aspirin or ibuprofen for 18 h, and then the cells were harvested by gentle pipetting. The expression levels of class I and class II MHC molecules were assessed using anti-H-2Kb and anti-I-Ab monoclonal antibodies. Shaded histograms represent the expression levels of H-2Kb and I-Ab molecules in DC2.4 cells cultured in the absence of the drugs. Thick line histograms represent the expression levels of H-2Kb and I-Ab molecules in DC2.4 cells cultured in the presence of the drugs.
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Figure 5: Effects of aspirin and ibuprofen on the expression of MHC molecules. DC2.4 cells were cultured with aspirin or ibuprofen for 18 h, and then the cells were harvested by gentle pipetting. The expression levels of class I and class II MHC molecules were assessed using anti-H-2Kb and anti-I-Ab monoclonal antibodies. Shaded histograms represent the expression levels of H-2Kb and I-Ab molecules in DC2.4 cells cultured in the absence of the drugs. Thick line histograms represent the expression levels of H-2Kb and I-Ab molecules in DC2.4 cells cultured in the presence of the drugs.

Mentions: To examine whether the suppressed capacity of aspirin or ibuprofen-treated DCs to present OVA peptides in association with MHC molecules was due to the inhibition of expression of MHC molecules on the cell surface, DC2.4 cells were cultured with the drugs (1 mg/ml) 18 h, and then the expression levels of MHC class I and class II molecules were determined by anti-H-2Kb and anti-I-Ab monoclonal antibodies. As shown in Fig. 5, aspirin did not affect the expression of MHC class I or class II molecules. Ibuprofen, which inhibited MHC-restricted exogenous OVA presentation, even slightly increased the expression of MHC class I and class II molecules. Flow cytometric analysis for major co-stimulatory molecules such as B7-1, B7-2, and CD40 also showed that aspirin did not affect the expression of these co-stimulatory molecules (Fig. 6). Again, ibuprofen, which inhibited MHC-restricted exogenous OVA presentation, even slightly increased the expression of co-stimulatory molecules such as B7-1, B7-2, and CD40 (Fig. 6).


Cyclooxygenase Inhibitors, Aspirin and Ibuprofen, Inhibit MHC-restricted Antigen Presentation in Dendritic Cells.

Kim HJ, Lee YH, Im SA, Kim K, Lee CK - Immune Netw (2010)

Effects of aspirin and ibuprofen on the expression of MHC molecules. DC2.4 cells were cultured with aspirin or ibuprofen for 18 h, and then the cells were harvested by gentle pipetting. The expression levels of class I and class II MHC molecules were assessed using anti-H-2Kb and anti-I-Ab monoclonal antibodies. Shaded histograms represent the expression levels of H-2Kb and I-Ab molecules in DC2.4 cells cultured in the absence of the drugs. Thick line histograms represent the expression levels of H-2Kb and I-Ab molecules in DC2.4 cells cultured in the presence of the drugs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2902675&req=5

Figure 5: Effects of aspirin and ibuprofen on the expression of MHC molecules. DC2.4 cells were cultured with aspirin or ibuprofen for 18 h, and then the cells were harvested by gentle pipetting. The expression levels of class I and class II MHC molecules were assessed using anti-H-2Kb and anti-I-Ab monoclonal antibodies. Shaded histograms represent the expression levels of H-2Kb and I-Ab molecules in DC2.4 cells cultured in the absence of the drugs. Thick line histograms represent the expression levels of H-2Kb and I-Ab molecules in DC2.4 cells cultured in the presence of the drugs.
Mentions: To examine whether the suppressed capacity of aspirin or ibuprofen-treated DCs to present OVA peptides in association with MHC molecules was due to the inhibition of expression of MHC molecules on the cell surface, DC2.4 cells were cultured with the drugs (1 mg/ml) 18 h, and then the expression levels of MHC class I and class II molecules were determined by anti-H-2Kb and anti-I-Ab monoclonal antibodies. As shown in Fig. 5, aspirin did not affect the expression of MHC class I or class II molecules. Ibuprofen, which inhibited MHC-restricted exogenous OVA presentation, even slightly increased the expression of MHC class I and class II molecules. Flow cytometric analysis for major co-stimulatory molecules such as B7-1, B7-2, and CD40 also showed that aspirin did not affect the expression of these co-stimulatory molecules (Fig. 6). Again, ibuprofen, which inhibited MHC-restricted exogenous OVA presentation, even slightly increased the expression of co-stimulatory molecules such as B7-1, B7-2, and CD40 (Fig. 6).

Bottom Line: In addition, the DCs generated in the presence of low concentrations of the drugs exhibit a profoundly suppressed capability to present MHC-restricted antigens.Aspirin and ibuprofen did not inhibit the phagocytic activity of DCs, the expression level of total MHC molecules and co-stimulatory molecules on DCs.These results demonstrate that aspirin and ibuprofen inhibit the intracellular processing event of the phagocytosed antigen, and further suggest that prolonged administration of NSAIDs in high doses may impair the capability of DCs to present antigens in asiociation with MHC molecules.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea.

ABSTRACT

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve pain, reduce fever and inhibit inflammation. NSAIDs function mainly through inhibition of cyclooxygenase (COX). Growing evidence suggests that NSAIDs also have immunomodulatory effects on T and B cells. Here we examined the effects of NSAIDs on the antigen presenting function of dendritic cells (DCs).

Methods: DCs were cultured in the presence of aspirin or ibuprofen, and then allowed to phagocytose biodegradable microspheres containing ovalbumin (OVA). After washing and fixing, the efficacy of OVA peptide presentation by DCs was evaluated using OVA-specific CD8 and CD4 T cells.

Results: Aspirin and ibuprofen at high concentrations inhibited both MHC class I and class II-restricted presentation of OVA in DCs. In addition, the DCs generated in the presence of low concentrations of the drugs exhibit a profoundly suppressed capability to present MHC-restricted antigens. Aspirin and ibuprofen did not inhibit the phagocytic activity of DCs, the expression level of total MHC molecules and co-stimulatory molecules on DCs. Ibuprofen rather increased the expression level of total MHC molecules and co-stimulatory molecules on DCs.

Conclusion: These results demonstrate that aspirin and ibuprofen inhibit the intracellular processing event of the phagocytosed antigen, and further suggest that prolonged administration of NSAIDs in high doses may impair the capability of DCs to present antigens in asiociation with MHC molecules.

No MeSH data available.


Related in: MedlinePlus