JNK1, but not JNK2, is required in two mechanistically distinct models of inflammatory arthritis

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Standard

JNK1, but not JNK2, is required in two mechanistically distinct models of inflammatory arthritis. / Denninger, Katja; Rasmussen, Susanne B; Larsen, Jeppe Madura; Ørskov, Cathrine; Seier Poulsen, Steen; Sørensen, Poul; Christensen, Jan Pravsgaard; Illges, Harald; Ødum, Niels; Labuda, Tord.

In: American Journal of Pathology, Vol. 179, No. 4, 2011, p. 1884-93.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Denninger, K, Rasmussen, SB, Larsen, JM, Ørskov, C, Seier Poulsen, S, Sørensen, P, Christensen, JP, Illges, H, Ødum, N & Labuda, T 2011, 'JNK1, but not JNK2, is required in two mechanistically distinct models of inflammatory arthritis', American Journal of Pathology, vol. 179, no. 4, pp. 1884-93. https://doi.org/10.1016/j.ajpath.2011.06.019

APA

Denninger, K., Rasmussen, S. B., Larsen, J. M., Ørskov, C., Seier Poulsen, S., Sørensen, P., Christensen, J. P., Illges, H., Ødum, N., & Labuda, T. (2011). JNK1, but not JNK2, is required in two mechanistically distinct models of inflammatory arthritis. American Journal of Pathology, 179(4), 1884-93. https://doi.org/10.1016/j.ajpath.2011.06.019

Vancouver

Denninger K, Rasmussen SB, Larsen JM, Ørskov C, Seier Poulsen S, Sørensen P et al. JNK1, but not JNK2, is required in two mechanistically distinct models of inflammatory arthritis. American Journal of Pathology. 2011;179(4):1884-93. https://doi.org/10.1016/j.ajpath.2011.06.019

Author

Denninger, Katja ; Rasmussen, Susanne B ; Larsen, Jeppe Madura ; Ørskov, Cathrine ; Seier Poulsen, Steen ; Sørensen, Poul ; Christensen, Jan Pravsgaard ; Illges, Harald ; Ødum, Niels ; Labuda, Tord. / JNK1, but not JNK2, is required in two mechanistically distinct models of inflammatory arthritis. In: American Journal of Pathology. 2011 ; Vol. 179, No. 4. pp. 1884-93.

Bibtex

@article{349d1793554c46a8a0c3a07c0a7b1a06,

title = "JNK1, but not JNK2, is required in two mechanistically distinct models of inflammatory arthritis",

abstract = "The roles of the c-Jun N-terminal kinases (JNKs) in inflammatory arthritis have been investigated; however, the roles of each isotype (ie, JNK1 and JNK2) in rheumatoid arthritis and conclusions about whether inhibition of one or both is necessary for amelioration of disease are unclear. By using JNK1- or JNK2-deficient mice in the collagen-induced arthritis and the KRN T-cell receptor transgenic mouse on C57BL/6 nonobese diabetic (K/BxN) serum transfer arthritis models, we demonstrate that JNK1 deficiency results in protection from arthritis, as judged by clinical score and histological evaluation in both models of inflammatory arthritis. In contrast, abrogation of JNK2 exacerbates disease. In collagen-induced arthritis, the distinct roles of the JNK isotypes can, at least in part, be explained by altered regulation of CD86 expression in JNK1- or JNK2-deficient macrophages in response to microbial products, thereby affecting T-cell-mediated immunity. The protection from K/BxN serum-induced arthritis in Jnk1(-/-) mice can also be explained by inept macrophage function because adoptive transfer of wild-type macrophages to Jnk1(-/-) mice restored disease susceptibility. Thus, our results provide a possible explanation for the modest therapeutic effects of broad JNK inhibitors and suggest that future therapies should selectively target the JNK1 isoform.",

author = "Katja Denninger and Rasmussen, {Susanne B} and Larsen, {Jeppe Madura} and Cathrine {\O}rskov and {Seier Poulsen}, Steen and Poul S{\o}rensen and Christensen, {Jan Pravsgaard} and Harald Illges and Niels {\O}dum and Tord Labuda",

year = "2011",

doi = "10.1016/j.ajpath.2011.06.019",

language = "English",

volume = "179",

pages = "1884--93",

journal = "American Journal of Pathology",

issn = "0002-9440",

publisher = "Elsevier",

number = "4",

}

RIS

TY - JOUR

T1 - JNK1, but not JNK2, is required in two mechanistically distinct models of inflammatory arthritis

AU - Denninger, Katja

AU - Rasmussen, Susanne B

AU - Larsen, Jeppe Madura

AU - Ørskov, Cathrine

AU - Seier Poulsen, Steen

AU - Sørensen, Poul

AU - Christensen, Jan Pravsgaard

AU - Illges, Harald

AU - Ødum, Niels

AU - Labuda, Tord

PY - 2011

Y1 - 2011

N2 - The roles of the c-Jun N-terminal kinases (JNKs) in inflammatory arthritis have been investigated; however, the roles of each isotype (ie, JNK1 and JNK2) in rheumatoid arthritis and conclusions about whether inhibition of one or both is necessary for amelioration of disease are unclear. By using JNK1- or JNK2-deficient mice in the collagen-induced arthritis and the KRN T-cell receptor transgenic mouse on C57BL/6 nonobese diabetic (K/BxN) serum transfer arthritis models, we demonstrate that JNK1 deficiency results in protection from arthritis, as judged by clinical score and histological evaluation in both models of inflammatory arthritis. In contrast, abrogation of JNK2 exacerbates disease. In collagen-induced arthritis, the distinct roles of the JNK isotypes can, at least in part, be explained by altered regulation of CD86 expression in JNK1- or JNK2-deficient macrophages in response to microbial products, thereby affecting T-cell-mediated immunity. The protection from K/BxN serum-induced arthritis in Jnk1(-/-) mice can also be explained by inept macrophage function because adoptive transfer of wild-type macrophages to Jnk1(-/-) mice restored disease susceptibility. Thus, our results provide a possible explanation for the modest therapeutic effects of broad JNK inhibitors and suggest that future therapies should selectively target the JNK1 isoform.

AB - The roles of the c-Jun N-terminal kinases (JNKs) in inflammatory arthritis have been investigated; however, the roles of each isotype (ie, JNK1 and JNK2) in rheumatoid arthritis and conclusions about whether inhibition of one or both is necessary for amelioration of disease are unclear. By using JNK1- or JNK2-deficient mice in the collagen-induced arthritis and the KRN T-cell receptor transgenic mouse on C57BL/6 nonobese diabetic (K/BxN) serum transfer arthritis models, we demonstrate that JNK1 deficiency results in protection from arthritis, as judged by clinical score and histological evaluation in both models of inflammatory arthritis. In contrast, abrogation of JNK2 exacerbates disease. In collagen-induced arthritis, the distinct roles of the JNK isotypes can, at least in part, be explained by altered regulation of CD86 expression in JNK1- or JNK2-deficient macrophages in response to microbial products, thereby affecting T-cell-mediated immunity. The protection from K/BxN serum-induced arthritis in Jnk1(-/-) mice can also be explained by inept macrophage function because adoptive transfer of wild-type macrophages to Jnk1(-/-) mice restored disease susceptibility. Thus, our results provide a possible explanation for the modest therapeutic effects of broad JNK inhibitors and suggest that future therapies should selectively target the JNK1 isoform.

U2 - 10.1016/j.ajpath.2011.06.019

DO - 10.1016/j.ajpath.2011.06.019

M3 - Journal article

C2 - 21839715

VL - 179

SP - 1884

EP - 1893

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 4

ER -

ID: 35354759

Department of Biomedical Sciences