Complement component 3 prevents imiquimod-induced psoriatic skin inflammation by inhibiting apoptosis in mice

Zheng, Quan‐you; Liang, Shen-Ju; Xu, Feng; Yang, Yi; Feng, Jianli; Shen, Fen De; Zhong, Yu; Wu, Shouzhen; Shu, Yongqian; Sun, Dao-dong; Xu, Guiping

doi:10.1016/j.intimp.2020.106692

Cited by 8 publications

(11 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, augmented JNK activation in the context of C3KD and CSE treatment was confirmed by western blotting ( Figures 6A, B ). Other studies have shown that C3 attenuates imiquimod-induced psoriatic skin inflammation by regulating apoptosis-associated proteins (Bak, cleaved caspase 3, and cytochrome c) in mice ( 27 ), and colligation of the B cell Ag receptor with the C3-binding CD21/CD19/CD81 costimulatory complex enhances the escape of human B cells from Fas-induced death by regulating the expression of molecules required for death-inducing signal complex formation (Fas, FADD, and caspase 8) ( 28 ). Therefore, we further measured apoptosis-associated proteins in CSE-induced 16HBE cells by western blotting.…”

Section: Resultsmentioning

confidence: 99%

Complement component 3 protects human bronchial epithelial cells from cigarette smoke-induced oxidative stress and prevents incessant apoptosis

Pei

Zhang

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

The complement component 3 (C3) is a pivotal element of the complement system and plays an important role in innate immunity. A previous study showed that intracellular C3 was upregulated in airway epithelial cells (AECs) from individuals with end-stage chronic obstructive pulmonary disease (COPD). Accumulating evidence has shown that cigarette smoke extract (CSE) induces oxidative stress and apoptosis in AECs. Therefore, we investigated whether C3 modulated cigarette smoke-induced oxidative stress and apoptosis in AECs and participated in the pathogenesis of COPD. We found increased C3 expression, together with increased oxidative stress and apoptosis, in a cigarette smoke-induced mouse model of COPD and in AECs from patients with COPD. Different concentrations of CSEinduced C3 expression in 16HBE cells in vitro. Interestingly, C3 knockdown (KD) exacerbated oxidative stress and apoptosis in 16HBE cells exposed to CSE. Furthermore, C3 exerted its pro-survival effects through JNK inhibition, while exogenous C3 partially rescued CSE-induced cell death and oxidative stress in C3 KD cells. These data indicate that locally produced C3 is an important pro-survival molecule in AECs under cigarette smoke exposure, revealing a potentially novel mechanism in the pathogenesis of COPD.

show abstract

Section: Resultsmentioning

confidence: 99%

Complement component 3 protects human bronchial epithelial cells from cigarette smoke-induced oxidative stress and prevents incessant apoptosis

Pei

Zhang

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…29 However, Zheng et al demonstrated that C3 deficiency led to significant aggravation of psoriatic skin lesions, as well as increased skin cell apoptosis and interferon-γ + T cell responses, suggesting that C3 deficiency deteriorated IMQ-induced psoriasis skin inflammation by facilitating apoptosis. 30 These opposite results may reflect differences in the duration of IMQ treatment or different effects of the downstream products during complement activation. C3 is cleaved into the small molecule, C3a, which binds to C3aR receptors in different cells to play downstream roles.…”

Section: Discussionmentioning

confidence: 99%

“…Giacomassi et al demonstrated that C3 was involved in the development and resolution of IMQ‐induced psoriasiform skin inflammation, which indicated that C3 played a proinflammatory role during psoriasis‐like skin inflammation 29 . However, Zheng et al demonstrated that C3 deficiency led to significant aggravation of psoriatic skin lesions, as well as increased skin cell apoptosis and interferon‐γ + T cell responses, suggesting that C3 deficiency deteriorated IMQ‐induced psoriasis skin inflammation by facilitating apoptosis 30 …”

Section: Discussionmentioning

confidence: 99%

Activation of the C3a anaphylatoxin receptor inhibits keratinocyte proliferation by regulating keratin 6, keratin 16, and keratin 17 in psoriasis

et al. 2022

View full text Add to dashboard Cite

Emerging evidence suggests that signaling through the C3a anaphylatoxin receptor (C3aR) protects against various inflammation‐related diseases. However, the role of C3aR in psoriasis remains unknown. The purpose of this study was to investigate the possible protective role of C3aR in psoriasis and to explore the underlying molecular mechanisms. We initially found that the psoriatic epidermis exhibited significantly decreased C3aR expression. C3aR showed protective roles in mouse models of imiquimod (IMQ)‐ and interleukin‐23‐induced psoriasis. Furthermore, increased epidermal thickness and keratin 6 (K6), K16, and K17 expression occurred in the ears and backs of C3aR−/− mice. Pharmacological treatment with a C3aR agonist ameliorated IMQ‐induced psoriasiform lesions in mice and decreased the expression of K6, K16, and K17. Additionally, the signal transducer and activator of transcription 3 (STAT3) pathway participated in the protective function of C3aR. More importantly, the expression levels of K6, K16, and K17 in keratinocytes were all restored in HaCaT cells transfected with a C3aR‐overexpression plasmid after treating them with colivelin (a STAT3 activator). Our findings demonstrate that C3aR protects against the development of psoriasis and suggest that C3aR confers protection by negatively regulating K6, K16, and K17 expression in a STAT3‐dependent manner, thus inhibiting keratinocyte proliferation and helping reverse the pathogenesis of psoriasis.

show abstract

“…35 The absence of C3 exacerbated the inflammatory phenotype by upregulating IFNγ + T-cell responses, and the phenotype was reversed by caspase inhibition, indicating that C3 exerts its protective role by inhibiting apoptosis. 35 Among the numerous physiological functions of C3 that remain unclear, C3 has been involved in apoptosis and angiogenesis regulation. In a model of retinopathy of prematurity, C3−/− mice displayed increased neovascularization, 36 and in a model of muscle ischemia, angiogenesis was associated with increased neutrophil and macrophage infiltration.…”

Section: Protectiveroleofc3mentioning

confidence: 97%

C3‐dependent effector functions of complement

Zarantonello

Revel

Grünenwald

et al. 2022

Immunological Reviews

View full text Add to dashboard Cite

The growing interest in recent years has put the complement system, part of the innate immune response, in the spotlight. Many novel functions of the complement system have been discovered, exceeding the limits of its bactericidal activity and complementing the action of antibodies. Biochemical and biophysical studies are the foundations of research in the complement system field. Over the years, accumulating evidence has contributed to the precise knowledge of the molecular mechanisms governing the complement system available to us today. Complement component C3 is considered the "Swiss Army Knife" of innate immunity and host defense and for a good reason. 1 In this review, we will outline the main C3 functions and how they are carried out through interactions with complement receptors. | C3-WhatisitandwheretofinditC3 is the central component of the complement system, present in the blood in concentrations of more than 1 mg/mL, which makes it one of the most represented proteins in circulation. Native C3 is considered biologically inactive, but its activation fragments have a multitude of biological functions. A plethora of structure-function

show abstract

Complement component 3 prevents imiquimod-induced psoriatic skin inflammation by inhibiting apoptosis in mice

Cited by 8 publications

References 44 publications

Complement component 3 protects human bronchial epithelial cells from cigarette smoke-induced oxidative stress and prevents incessant apoptosis

Complement component 3 protects human bronchial epithelial cells from cigarette smoke-induced oxidative stress and prevents incessant apoptosis

Activation of the C3a anaphylatoxin receptor inhibits keratinocyte proliferation by regulating keratin 6, keratin 16, and keratin 17 in psoriasis

C3‐dependent effector functions of complement

Contact Info

Product

Resources

About