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Bafilomycin A1 enhances the production of IL‐1b induced by the proteasome inhibitor MG‐132 but not that of IL‐8
Author(s) -
PIIPPO N,
HYTTI M,
KINNUNEN K,
SALMINEN A,
KAARNIRANTA K,
KAUPPINEN A
Publication year - 2013
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2013.t003.x
Subject(s) - bafilomycin , autophagy , inflammasome , proteasome , microbiology and biotechnology , intracellular , protein degradation , inflammation , chemistry , degradation (telecommunications) , biology , biochemistry , immunology , apoptosis , telecommunications , computer science
Purpose Autophagy and proteasomal degradation, two central clearance systems of the cell, decline during aging. Increased amount of protein aggregates and other waste material compromise normal cellular functions. Inflammasomes are intracellular protein complexes which can become activated by diverse danger signals. It has recently been shown that a decline in cellular clearance systems can offer a sufficient signal for the inflammasome activation. In the present study, we have studied the effects of impaired proteasomal degradation and autophagy on inflammation in ARPE‐19 cells. Methods In order to inhibit the proteasomal degradation and autophagy, ARPE‐19 cells were treated with MG‐132 and Bafilomycin A1, respectively. Productions of IL‐1b and IL‐8 were measured using ELISA method. Results Our data shows that MG‐132 increases the productions of IL‐1b and IL‐8. The addition of Bafilomycin A1 further increases the amount of IL‐1b but not that of IL‐8. Conclusion Our data suggests that intracellular protein aggregates are capable of inducing inflammation through several pathways. Production of IL‐1b indicates the activation of inflammasome signaling. Interestingly, the inflammasome signaling seems to become further enhanced when autophagy is blocked in addition to proteasomes. Meanwhile, the production of IL‐8 remains at the same level.

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