Interleukin-24 Immunobiology and Its Roles in Inflammatory Diseases

Zhong, Yajie; Zhang, Xuan; Chong, Wai Po

doi:10.3390/ijms23020627

Cited by 22 publications

(17 citation statements)

References 66 publications

(90 reference statements)

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“…IL-24 has been demonstrated to regulate tissue inflammation via IL-24 receptor expression in epithelial cells, such as in keratinocytes in psoriasis and colonic epithelial cells in inflammatory bowel disease [ 9 ]. Therefore, we studied the effect of IL-24 on the expression of proinflammatory molecules in the retinas of IL-24-treated, inflamed eyes of EAU mice.…”

Section: Resultsmentioning

confidence: 99%

“…To investigate whether IL-24 could also regulate human RPE cells, we first studied the expression of IL-24 receptors. IL-24 signal through two heterodimeric receptors, i.e., IL-20RB/IL-20RA and IL-20RB/IL-22RA1 [ 9 ]. We found that the human RPE cell line, ARPE-19, expressed high levels of IL-20RA and IL-22RA1 ( Figure 5 A).…”

Section: Resultsmentioning

confidence: 99%

“…Together with IL-19 and IL-20, these are known as IL-20 receptor cytokines because their receptors are comprised of the IL-20 receptor β-subunit (IL-20RB) [ 8 ]. IL-24 has two heterodimeric receptors, i.e., IL-20RB, with either the IL-20 receptor α-subunit (IL-20RA) or the IL-22 receptor α1-subunit (IL-22RA1) [ 9 ]. IL-24 and its receptors are widely expressed by immune cells and epithelial cells, and IL-24 elevation is associated with different autoimmune diseases, including psoriasis [ 10 ], rheumatoid arthritis [ 11 ], inflammatory bowel diseases [ 12 ], and multiple sclerosis [ 13 ], suggesting that it is a multifunctional cytokine that may play a critical role in regulating tissue inflammation and autoimmunity.…”

Section: Introductionmentioning

confidence: 99%

“…IL-24 is produced by different immune cells, including T cells, B cells, natural killer (NK) cells, monocytes, and macrophages [ 9 ]. It has been shown to be a Th2 cytokine [ 14 ], inhibiting the production of interferon (IFN)-γ and IL-17A from Th1 and Th17 cells, respectively [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Multifunctional Interleukin-24 Resolves Neuroretina Autoimmunity via Diverse Mechanisms

Zhang

Zhong

et al. 2022

IJMS

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IL-24 is a multifunctional cytokine that regulates both immune cells and epithelial cells. Although its elevation is associated with a number of autoimmune diseases, its tolerogenic properties against autoreactive T cells have recently been revealed in an animal model of central nervous system (CNS) autoimmunity by inhibiting the pathogenic Th17 response. To explore the potential of IL-24 as a therapeutic agent in CNS autoimmunity, we induced experimental autoimmune uveitis (EAU) in wildtype mice and intravitreally injected IL-24 into the inflamed eye after disease onset. We found that the progression of ocular inflammation was significantly inhibited in the IL-24-treated eye when compared to the control eye. More importantly, IL-24 treatment suppressed cytokine production from ocular-infiltrating, pathogenic Th1 and Th17 cells. In vitro experiments confirmed that IL-24 suppressed both Th1 and Th17 differentiation by regulating their master transcription factors T-bet and RORγt, respectively. In addition, we found that intravitreal injection of IL-24 suppressed the production of proinflammatory cytokines and chemokines from the retinas of the EAU-inflamed eyes. This observation appears to be applicable in humans, as IL-24 similarly inhibits human retinal pigment epithelium cells ARPE-19. In conclusion, we report here that IL-24, as a multifunctional cytokine, is capable of resolving ocular inflammation in EAU mice by targeting both uveitogenic T cells and RPE cells. This study sheds new light on IL-24 as a potential therapeutic candidate for autoimmune uveitis.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Multifunctional Interleukin-24 Resolves Neuroretina Autoimmunity via Diverse Mechanisms

Zhang

Zhong

et al. 2022

IJMS

Self Cite

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“…The IL-19 gene is located next to the IL-10 telomere region on chromosome 1q32 and is produced by monocytes and, to a lesser extent, by B cells. The role of IL-19 as an anti-inflammatory agent in various disorders such as respiratory, liver, and autoimmune diseases has been investigated (14). On the other hand, the role of IL-19 in causing the inflammatory response in infections has also been proven.…”

Section: Introductionmentioning

confidence: 99%

Association between interleukin-19 gene polymorphisms and maternal puerperal infection

Sang¹,

Tan²,

Wu³

et al. 2022

Cell Mol Biol (Noisy-le-grand)

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Any bacterial infection of the genital tract after childbirth is called maternal puerperal infection. This infection accounts for 13% of pregnancy-related deaths and is the fifth leading cause of maternal mortality. Endometritis (postpartum uterine infection) has been associated with preeclampsia and maternal lethal bleeding in recent decades. In some studies, the presence of meconium in the amniotic fluid has been implicated in the development of endometritis. The study aimed to evaluate the association between interleukin-19 gene polymorphisms and maternal puerperal infection. In this study, 300 pregnant women with a gestational age of at least 37 weeks were studied. Patients were divided into two groups of 150 controls and cases. In the case group, amniotic fluid was impregnated with meconium, and in the control group, it was clear fluid. Both groups underwent cesarean section, and all received prophylactic antibiotics before surgery. Patients were evaluated for purpura infection in the first 40 days after delivery. Five ml of venous blood was taken from each patient and transferred to a tube containing EDTA anticoagulant. Genomic DNA was isolated using a particular kit. Then, the polymerase chain reaction was performed by the ARMS method. Data were analyzed using the chisquare test and SPSS software version 19 in case and control groups. This study's results indicate no significant difference in the frequency of AG, GG, and AA genotypes at position rs2243191 and rs1028181 IL-19 gene polymorphism between patients with puerperal infection and the control group (P>0.05). Also, no significant difference was observed in the frequency of both G and A alleles in the mentioned situations between patients and the control group (P>0.05). Based on the results of this study, no significant relationship was observed between IL-19 gene polymorphism at rs2243191 and rs1028181 locus and puerperal infection.

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PIKFYVE inhibitors trigger interleukin‐24‐dependent cell death of autophagy‐dependent melanoma

Roy,

Chakraborty,

DePamphilis

2024

Molecular Oncology

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Inhibitors specifically targeting the 1‐phosphatidylinositol 3‐phosphate 5‐kinase (PIKFYVE) disrupt lysosome homeostasis, thereby selectively terminating autophagy‐dependent human cancer cells in vivo as well as in vitro without harming the viability of nonmalignant cells. To elucidate the mechanism by which PIKFYVE inhibition induces cell death, autophagy‐dependent melanoma cells were compared with normal foreskin fibroblasts. RNA sequence profiling suggested that PIKFYVE inhibitors upregulated an endoplasmic reticulum (ER) stress response involving interleukin‐24 (IL24; also known as MDA7) selectively in melanoma cells. Subsequent biochemical and genetic analyses confirmed these results and extended them to tumor xenografts in which tumor formation and expansion were inhibited. IL24 expression was upregulated by the DDIT3/CHOP/CEBPz transcription factor, a component of the PERK‐dependent ER‐stress response. Ectopic expression of IL24‐induced cell death in melanoma cells, but not in foreskin fibroblasts, whereas ablation of the IL24 gene in melanoma cells prevented death. IL24 upregulation was triggered specifically by PIKFYVE inhibition. Thus, unlike thapsigargin and tunicamycin, which induce ER‐stress indiscriminately, PIKFYVE inhibitors selectively terminated PIKFYVE‐sensitive melanoma by inducing IL24‐dependent ER‐stress. Moreover, induction of cell death by a PIKFYVE inhibitor together with ectopic expression of IL24 protein was cumulative, thereby confirming the therapeutic potential of PIKFYVE inhibitors in the treatment of melanoma.

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Interleukin-24 Immunobiology and Its Roles in Inflammatory Diseases

Cited by 22 publications

References 66 publications

Multifunctional Interleukin-24 Resolves Neuroretina Autoimmunity via Diverse Mechanisms

Multifunctional Interleukin-24 Resolves Neuroretina Autoimmunity via Diverse Mechanisms

Association between interleukin-19 gene polymorphisms and maternal puerperal infection

PIKFYVE inhibitors trigger interleukin‐24‐dependent cell death of autophagy‐dependent melanoma

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