14-3-3 modulation of the inflammatory response

Munier, Claire C; Ottmann, C.; Perry, Matthew W. D.

doi:10.1016/j.phrs.2020.105236

Cited by 48 publications

(37 citation statements)

References 118 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As it is well known, these arise from defective or inappropriate immune responses but are sustained and complicated in their progression by degenerative processes moved by chronic inflammatory events. Therefore, in autoimmune disorders, the main pharmacological practices target inflammatory cytokines and their intracellular signalling pathways [21]. Accordingly, trials to assess the efficacy of anti-rheumatic therapies, such as hydroxychloroquine, and anti-cytokine therapies, such as interleukin (IL)-6 inhibitors for improving outcomes in COVID-19 patients are still ongoing [22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

How Do Inflammatory Mediators, Immune Response and Air Pollution Contribute to COVID-19 Disease Severity? A Lesson to Learn

Signorini

Pignatti

Coccini

2021

Life

View full text Add to dashboard Cite

Inflammatory and immune processes are defensive mechanisms that aim to remove harmful agents. As a response to infections, inflammation and immune response contribute to the pathophysiological mechanisms of diseases. Coronavirus disease 2019 (COVID-19), whose underlying mechanisms remain not fully elucidated, has posed new challenges for the knowledge of pathophysiology. Chiefly, the inflammatory process and immune response appear to be unique features of COVID-19 that result in developing a hyper-inflammatory syndrome, and air pollution, the world’s largest health risk factor, may partly explain the behaviour and fate of COVID-19. Understanding the mechanisms involved in the progression of COVID-19 is of fundamental importance in order to avoid the late stage of the disease, associated with a poor prognosis. Here, the role of the inflammatory and immune mediators in COVID-19 pathophysiology is discussed.

show abstract

Section: Introductionmentioning

confidence: 99%

How Do Inflammatory Mediators, Immune Response and Air Pollution Contribute to COVID-19 Disease Severity? A Lesson to Learn

Signorini

Pignatti

Coccini

2021

Life

View full text Add to dashboard Cite

show abstract

“…The 14-3-3ζ protein is a vital adaptor protein regulating several cellular processes including immune responses (26,45,46). Our study shows that 14-3-3ζ has an arthritis-suppressive function in LEW rats.…”

Section: Discussionmentioning

confidence: 59%

14-3-3ζ: A suppressor of inflammatory arthritis

Kim

Chun

McGowan

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Inflammatory arthritis (IA) is a common disease that affects millions of individuals worldwide. Proinflammatory events during IA pathogenesis are well studied; however, loss of protective immunity remains underexplored. Earlier, we reported that 14-3-3zeta (ζ) has a role in T-cell polarization and interleukin (IL)-17A signal transduction. Here, we demonstrate that 14-3-3ζ knockout (KO) rats develop early-onset severe arthritis in two independent models of IA, pristane-induced arthritis and collagen-induced arthritis. Arthritic 14-3-3ζ KO animals showed an increase in bone loss and immune cell infiltration in synovial joints. Induction of arthritis coincided with the loss of anti-14-3-3ζ antibodies; however, rescue experiments to supplement the 14-3-3ζ antibody by passive immunization did not suppress arthritis. Instead, 14-3-3ζ immunization during the presymptomatic phase resulted in significant suppression of arthritis in both wild-type and 14-3-3ζ KO animals. Mechanistically, 14-3-3ζ KO rats exhibited elevated inflammatory gene signatures at the messenger RNA and protein levels, particularly for IL-1β. Furthermore, the immunization with recombinant 14-3-3ζ protein suppressed IL-1β levels, significantly increased anti-14-3-3ζ antibody levels and collagen production, and preserved bone quality. The 14-3-3ζ protein increased collagen expression in primary rat mesenchymal cells. Together, our findings indicate that 14-3-3ζ causes immune suppression and extracellular remodeling, which lead to a previously unrecognized IA-suppressive function.

show abstract

“…In previous reports, AKT2 can act as an anchor and cooperate with 14‐3‐3 to restrain the transcription‐related factor p27 Kip1 in cytoplasm (Fujita et al , 2002; Sekimoto et al , 2004). Based on the abundant expression of the 14‐3‐3 family members, that is, 14‐3‐3ε (14‐3‐3epsilon, 14‐3‐3Ε) and 14‐3‐3ζ (14‐3‐3zeta, 14‐3‐3Ζ) in macrophages (Munier et al , 2002), we performed IP and found that both 14‐3‐3ε and 14‐3‐3ζ interacted with AKT2 (Fig EV3H). We further explored whether 14‐3‐3ε and 14‐3‐3ζ might assist AKT2 to regulate the cellular location of IRF3 and expression of Ifnb1 .…”

Section: Resultsmentioning

confidence: 99%

AKT2 reduces IFNβ1 production to modulate antiviral responses and systemic lupus erythematosus

et al. 2022

View full text Add to dashboard Cite

Interferon regulatory factor 3 (IRF3)‐induced type I interferon (I‐IFN) production plays key roles in both antiviral and autoimmune responses. IRF3 phosphorylation, dimerization, and nuclear localization are needed for its activation and function, but the precise regulatory mechanisms remain to be explored. Here, we show that the serine/threonine kinase AKT2 interacts with IRF3 and phosphorylates it on Thr207, thereby attenuating IRF3 nuclear translocation in a 14‐3‐3ε‐dependent manner and reducing I‐IFN production. We further find that AKT2 expression is downregulated in viral‐infected macrophages or in monocytes and tissue samples from systemic lupus erythematosus (SLE) patients and mouse models. Akt2‐deficient mice exhibit increased I‐IFN induction and reduced mortality in response to viral infection, but aggravated severity of SLE. Overexpression of AKT2 kinase‐inactive or IRF3‐T207A mutants in zebrafish supports that AKT2 negatively regulates I‐IFN production and antiviral response in a kinase‐dependent manner. This negative role of AKT2 in IRF3‐induced I‐IFN production suggests that AKT2 may be therapeutically targeted to differentially regulate antiviral infection and SLE.

show abstract

14-3-3 modulation of the inflammatory response

Cited by 48 publications

References 118 publications

How Do Inflammatory Mediators, Immune Response and Air Pollution Contribute to COVID-19 Disease Severity? A Lesson to Learn

How Do Inflammatory Mediators, Immune Response and Air Pollution Contribute to COVID-19 Disease Severity? A Lesson to Learn

14-3-3ζ: A suppressor of inflammatory arthritis

AKT2 reduces IFNβ1 production to modulate antiviral responses and systemic lupus erythematosus

Contact Info

Product

Resources

About