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The severity of experimental arthritis is independent of IL-36 receptor signaling.

Lamacchia C, Palmer G, Rodriguez E, Martin P, Vigne S, Seemayer CA, Talabot-Ayer D, Towne JE, Gabay C - Arthritis Res. Ther. (2013)

Bottom Line: IL-36 exerts proinflammatory effects in skin and lung and stimulates T cell responses.As opposed to anti-IL-1RI antibody treatment, the injection of an anti-IL-36R antibody was devoid of effect on the development and severity of CIA.The severity of joint inflammation and structural damage in AIA was also unaltered by anti-IL-36R antibody treatment.

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ABSTRACT

Introduction: Interleukin (IL)-36 refers to three related IL-1 family cytokines, IL-36α, IL-36β, and IL-36γ, that bind to the IL-36 receptor (IL-36R). IL-36 exerts proinflammatory effects in skin and lung and stimulates T cell responses. In the present study, we examined the expression and function of IL-36R and its ligands in experimental arthritis.

Methods: Collagen-induced arthritis (CIA), antigen-induced arthritis (AIA), and K/BxN serum transfer-induced arthritis were induced according to standard protocols. Messenger RNA levels for IL-36R and its ligands in the joints of mice with CIA were determined by RT-qPCR. Mice with CIA were injected with a blocking monoclonal anti-IL-36R, a blocking anti-IL-1RI, or their isotype-matched control antibodies at the time of arthritis onset. Anti-IL-36R or control antibodies were also injected at the time of AIA induction. Finally, IL-36R-deficient mice were examined in AIA and serum transfer-induced arthritis. The development and severity of arthritis were assessed by clinical and histological scoring.

Results: IL-36R, IL-36Ra and IL-36γ mRNA were detected in the joints of mice with CIA, but their levels did not correlate with arthritis severity. As opposed to anti-IL-1RI antibody treatment, the injection of an anti-IL-36R antibody was devoid of effect on the development and severity of CIA. The severity of joint inflammation and structural damage in AIA was also unaltered by anti-IL-36R antibody treatment. Finally, the severity of AIA and K/BxN serum transfer-induced arthritis was similar in IL-36R-deficient and wild-type mice.

Conclusions: The development and severity of experimental arthritis are independent of IL-36R signaling.

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Incidence and severity of K/BxN serum transfer-induced arthritis are not reduced in IL-36 receptor (R) knockout (KO) mice. Incidence of arthritis (A), arthritis severity scores (B) and the number of affected paws (C) are shown for WT (n = 10, black line) and IL-36R KO (n = 7, dashed line) mice. (A and C) Results are shown as the mean ± standard error of the mean.
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Figure 5: Incidence and severity of K/BxN serum transfer-induced arthritis are not reduced in IL-36 receptor (R) knockout (KO) mice. Incidence of arthritis (A), arthritis severity scores (B) and the number of affected paws (C) are shown for WT (n = 10, black line) and IL-36R KO (n = 7, dashed line) mice. (A and C) Results are shown as the mean ± standard error of the mean.

Mentions: CIA and AIA are dependent on active immunization and are therefore influenced by alterations of the adaptive immune response. To more specifically investigate the involvement of IL-36R in the inflammatory effector phase of arthritis, we used the passive K/BxN serum transfer-induced model, which is independent of the adaptive immune response in IL-36R-/- and WT control mice. As shown in Figure 5, we observed no difference in the incidence and the severity of the disease between IL-36R-/- and wild-type mice.


The severity of experimental arthritis is independent of IL-36 receptor signaling.

Lamacchia C, Palmer G, Rodriguez E, Martin P, Vigne S, Seemayer CA, Talabot-Ayer D, Towne JE, Gabay C - Arthritis Res. Ther. (2013)

Incidence and severity of K/BxN serum transfer-induced arthritis are not reduced in IL-36 receptor (R) knockout (KO) mice. Incidence of arthritis (A), arthritis severity scores (B) and the number of affected paws (C) are shown for WT (n = 10, black line) and IL-36R KO (n = 7, dashed line) mice. (A and C) Results are shown as the mean ± standard error of the mean.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672771&req=5

Figure 5: Incidence and severity of K/BxN serum transfer-induced arthritis are not reduced in IL-36 receptor (R) knockout (KO) mice. Incidence of arthritis (A), arthritis severity scores (B) and the number of affected paws (C) are shown for WT (n = 10, black line) and IL-36R KO (n = 7, dashed line) mice. (A and C) Results are shown as the mean ± standard error of the mean.
Mentions: CIA and AIA are dependent on active immunization and are therefore influenced by alterations of the adaptive immune response. To more specifically investigate the involvement of IL-36R in the inflammatory effector phase of arthritis, we used the passive K/BxN serum transfer-induced model, which is independent of the adaptive immune response in IL-36R-/- and WT control mice. As shown in Figure 5, we observed no difference in the incidence and the severity of the disease between IL-36R-/- and wild-type mice.

Bottom Line: IL-36 exerts proinflammatory effects in skin and lung and stimulates T cell responses.As opposed to anti-IL-1RI antibody treatment, the injection of an anti-IL-36R antibody was devoid of effect on the development and severity of CIA.The severity of joint inflammation and structural damage in AIA was also unaltered by anti-IL-36R antibody treatment.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: Interleukin (IL)-36 refers to three related IL-1 family cytokines, IL-36α, IL-36β, and IL-36γ, that bind to the IL-36 receptor (IL-36R). IL-36 exerts proinflammatory effects in skin and lung and stimulates T cell responses. In the present study, we examined the expression and function of IL-36R and its ligands in experimental arthritis.

Methods: Collagen-induced arthritis (CIA), antigen-induced arthritis (AIA), and K/BxN serum transfer-induced arthritis were induced according to standard protocols. Messenger RNA levels for IL-36R and its ligands in the joints of mice with CIA were determined by RT-qPCR. Mice with CIA were injected with a blocking monoclonal anti-IL-36R, a blocking anti-IL-1RI, or their isotype-matched control antibodies at the time of arthritis onset. Anti-IL-36R or control antibodies were also injected at the time of AIA induction. Finally, IL-36R-deficient mice were examined in AIA and serum transfer-induced arthritis. The development and severity of arthritis were assessed by clinical and histological scoring.

Results: IL-36R, IL-36Ra and IL-36γ mRNA were detected in the joints of mice with CIA, but their levels did not correlate with arthritis severity. As opposed to anti-IL-1RI antibody treatment, the injection of an anti-IL-36R antibody was devoid of effect on the development and severity of CIA. The severity of joint inflammation and structural damage in AIA was also unaltered by anti-IL-36R antibody treatment. Finally, the severity of AIA and K/BxN serum transfer-induced arthritis was similar in IL-36R-deficient and wild-type mice.

Conclusions: The development and severity of experimental arthritis are independent of IL-36R signaling.

Show MeSH
Related in: MedlinePlus