The genetic ablation of cyclooxygenase 2 prevents the development of autoimmune arthritis

Linda Myers, Andrew Kang, Arnold Postlethwaite, Edward F. Rosloniec, Scott G. Morham, Boris V. Shlopov, Sarita Goorha, Leslie R. Ballou

Research output: Contribution to journalArticle

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Abstract

Objective. To determine the effects of cyclooxygenase 1 (COX-1) and COX-2 gene deletion on collagen-induced arthritis (CIA). Methods. Mice that were susceptible to CIA but lacked either the COX-1 or the COX-2 gene were immunized with type II collagen (CII), and the incidence and severity of arthritis were compared with findings in wild-type animals, by clinical and histologic examination. The immune response was assessed by measuring total CII IgG, IgG1, and IgG2 antibody production in sera from immunized mice. The passive transfer of arthritis, accomplished using anti-CII monoclonal antibodies, was tested in wild-type and COX-deficient (-/-) mice. Splenocytes cultured from CII-immunized wild-type and COX-/- mice were challenged with bovine α1(II), and cytokine production was assessed. Results. COX-2 gene deletion reduced the incidence and severity of CIA compared with findings in wild-type and COX-1-/- mice. Histologic examination of joints after the onset of clinical arthritis revealed cartilage erosions, proliferation of the synovial lining, and inflammatory cell infiltration in wild-type and COX-1-/- mice, but not in COX-2-/- mice. COX-2-/- mice exhibited reduced anti-CII IgG antibody levels, indicating a decreased immune response. However, cytokine production by spleen cells from immunized mice indicated no cytokine deficiencies in COX-2-/- mice compared with wild-type or COX-1-/-mice. More important, arthritis could not be passively transferred to naive COX-2-/- mice, indicating a requirement for COX-2 in the pathogenesis of arthritis, independent of the immune response. Conclusion. COX-2-/- mice exhibit at least 2 defects resulting in down-modulation of the development of CIA: a reduced immune response to CII demonstrated by a markedly reduced antibody titer, and an 'inflammatory' defect reflected by the inability to passively transfer arthritis to COX-2-/- mice.

Original languageEnglish (US)
Pages (from-to)2687-2693
Number of pages7
JournalArthritis and Rheumatism
Volume43
Issue number12
DOIs
StatePublished - Dec 1 2000

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Cyclooxygenase 2
Arthritis
Cyclooxygenase 1
Experimental Arthritis
Immunoglobulin G
Gene Deletion
Cytokines
Wild Animals
Collagen Type II
Antibodies
Incidence
Cartilage
Antibody Formation
Spleen
Joints
Monoclonal Antibodies

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

The genetic ablation of cyclooxygenase 2 prevents the development of autoimmune arthritis. / Myers, Linda; Kang, Andrew; Postlethwaite, Arnold; Rosloniec, Edward F.; Morham, Scott G.; Shlopov, Boris V.; Goorha, Sarita; Ballou, Leslie R.

In: Arthritis and Rheumatism, Vol. 43, No. 12, 01.12.2000, p. 2687-2693.

Research output: Contribution to journalArticle

Myers, Linda ; Kang, Andrew ; Postlethwaite, Arnold ; Rosloniec, Edward F. ; Morham, Scott G. ; Shlopov, Boris V. ; Goorha, Sarita ; Ballou, Leslie R. / The genetic ablation of cyclooxygenase 2 prevents the development of autoimmune arthritis. In: Arthritis and Rheumatism. 2000 ; Vol. 43, No. 12. pp. 2687-2693.
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abstract = "Objective. To determine the effects of cyclooxygenase 1 (COX-1) and COX-2 gene deletion on collagen-induced arthritis (CIA). Methods. Mice that were susceptible to CIA but lacked either the COX-1 or the COX-2 gene were immunized with type II collagen (CII), and the incidence and severity of arthritis were compared with findings in wild-type animals, by clinical and histologic examination. The immune response was assessed by measuring total CII IgG, IgG1, and IgG2 antibody production in sera from immunized mice. The passive transfer of arthritis, accomplished using anti-CII monoclonal antibodies, was tested in wild-type and COX-deficient (-/-) mice. Splenocytes cultured from CII-immunized wild-type and COX-/- mice were challenged with bovine α1(II), and cytokine production was assessed. Results. COX-2 gene deletion reduced the incidence and severity of CIA compared with findings in wild-type and COX-1-/- mice. Histologic examination of joints after the onset of clinical arthritis revealed cartilage erosions, proliferation of the synovial lining, and inflammatory cell infiltration in wild-type and COX-1-/- mice, but not in COX-2-/- mice. COX-2-/- mice exhibited reduced anti-CII IgG antibody levels, indicating a decreased immune response. However, cytokine production by spleen cells from immunized mice indicated no cytokine deficiencies in COX-2-/- mice compared with wild-type or COX-1-/-mice. More important, arthritis could not be passively transferred to naive COX-2-/- mice, indicating a requirement for COX-2 in the pathogenesis of arthritis, independent of the immune response. Conclusion. COX-2-/- mice exhibit at least 2 defects resulting in down-modulation of the development of CIA: a reduced immune response to CII demonstrated by a markedly reduced antibody titer, and an 'inflammatory' defect reflected by the inability to passively transfer arthritis to COX-2-/- mice.",
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AU - Myers, Linda

AU - Kang, Andrew

AU - Postlethwaite, Arnold

AU - Rosloniec, Edward F.

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AU - Shlopov, Boris V.

AU - Goorha, Sarita

AU - Ballou, Leslie R.

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AB - Objective. To determine the effects of cyclooxygenase 1 (COX-1) and COX-2 gene deletion on collagen-induced arthritis (CIA). Methods. Mice that were susceptible to CIA but lacked either the COX-1 or the COX-2 gene were immunized with type II collagen (CII), and the incidence and severity of arthritis were compared with findings in wild-type animals, by clinical and histologic examination. The immune response was assessed by measuring total CII IgG, IgG1, and IgG2 antibody production in sera from immunized mice. The passive transfer of arthritis, accomplished using anti-CII monoclonal antibodies, was tested in wild-type and COX-deficient (-/-) mice. Splenocytes cultured from CII-immunized wild-type and COX-/- mice were challenged with bovine α1(II), and cytokine production was assessed. Results. COX-2 gene deletion reduced the incidence and severity of CIA compared with findings in wild-type and COX-1-/- mice. Histologic examination of joints after the onset of clinical arthritis revealed cartilage erosions, proliferation of the synovial lining, and inflammatory cell infiltration in wild-type and COX-1-/- mice, but not in COX-2-/- mice. COX-2-/- mice exhibited reduced anti-CII IgG antibody levels, indicating a decreased immune response. However, cytokine production by spleen cells from immunized mice indicated no cytokine deficiencies in COX-2-/- mice compared with wild-type or COX-1-/-mice. More important, arthritis could not be passively transferred to naive COX-2-/- mice, indicating a requirement for COX-2 in the pathogenesis of arthritis, independent of the immune response. Conclusion. COX-2-/- mice exhibit at least 2 defects resulting in down-modulation of the development of CIA: a reduced immune response to CII demonstrated by a markedly reduced antibody titer, and an 'inflammatory' defect reflected by the inability to passively transfer arthritis to COX-2-/- mice.

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