Janus kinase/signal transducers and activator of transcription (JAK/STAT) and its role in Lung inflammatory disease

doi:10.1016/j.cbi.2023.110334

Chemico-Biological Interactions

Volume 371, 1 February 2023, 110334

https://doi.org/10.1016/j.cbi.2023.110334 Get rights and content

Highlights

•
JAK/STAT signaling pathway is connected to type 1 and 2 cytokine receptors.
•
JAK/STAT sends extracellular information to the cell nucleus.
•
This review examines severe lung inflammation and the JAK/STAT signalling pathway's role.

Abstract

A key signaling channel for the signal transduction of several crucial cytokines implicated in sepsis is the JAK/STAT system. Once cytokines attach to the proper receptors, JAK kinases linked to them are activated and can selectively phosphorylate STATs. Activated STATs subsequently go to the nucleus, where they play a key role in the transcription of the target genes. Various biological activities use the JAK/STAT pathway, including hematopoiesis, immunological modulation, cell differentiation, and apoptosis. Inflammatory lung illnesses affect people worldwide and are a serious public health concern. Numerous common respiratory conditions, such as asthma, bronchiectasis, chronic obstructive pulmonary disease (COPD), and acute respiratory distress syndrome, are strongly influenced by inflammation. Microorganism infections or the destruction or demise of host cells are the causes of inflammation and the factors that perpetuate it. This review discusses the main elements of severe lung inflammation and how the JAK/STAT signaling pathway is essential for lung inflammation.

Introduction

A signaling pathway known as JAK/STAT is connected to type 1 and 2 cytokine receptors. Another name for it is the interlukin-6 (IL-6) signaling pathway. Several bodily processes, including cell division, proliferation, apoptosis, immunological control, and hematopoiesis, are regulated by the JAK/STAT system [1,2]. The JAK/STAT pathway transfers the information from the extracellular environment to the cell nucleus, where it activates transcription factors and starts biological processes [3]. Lung inflammatory disorders are a substantial public health concern on every continent of the world and greatly increase the socioeconomic burden of illness. Globally, these diseases are estimated to affect more than 510 million people [4,5]. Inflammation significantly impacts several respiratory conditions, including asthma, bronchiectasis, and COPD [6]. Inflammation significantly affects a variety of common respiratory disorders, including asthma, COPD, acute respiratory distress syndrome, and bronchiectasis [7]. Microorganism infections or the destruction or demise of host cells are the causes of inflammation and the factors that perpetuate it. Arthritis, diabetes, AIDS, atherosclerosis, inflammatory and immunological illnesses, and cancer of the important organs can all be brought on by abnormal regulation of the JAK/STAT protein [8,9].

Section snippets

History of JAK/STAT

The study of the JAK/STAT pathway started after the discovery of interferon in 1957; Chick embryo cells treated with the influenza virus reportedly generated tiny, virally inhibitory proteins that Alick Isaacs and Jean Lindenmann eventually termed interferon. After interferon was discovered, researchers were increasingly eager to learn how interferon triggered the activation of a transcription factor. Three decades later, in 1990, one article reported that interferon-stimulated gene factor 3

Lung inflammatory disease and JAK/STAT

Inflammation is an immunological reaction to infections, poisonous substances, damaged cells, or other irritants; it causes several biological processes; it's characterized by redness, swelling, heat, pain, and loss of cells [1,14]. Numerous main inflammatory stimuli, including cytokines, interleukin, tumor necrosis factor -alpha (TNF-α), and interferon, activate cell surface receptors before signaling pathway activation [21,22]. Different signaling pathways, including the nuclear factor-κB

Conclusion and future prospective

Asthma, lung cancer, obstructive pulmonary disease, and various other inflammatory respiratory disorders are directly caused by JAK/STAT pathways. Coronavirus and pulmonary TB are also significantly influenced by these pathways. These findings highlight the role of JAK/STAT signaling in the etiopathogenesis of inflammatory lung illnesses and act as an important research tool for developing new medications. Drug development for treating lung illness brought on by an inflammatory response will

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgement

KD is supported by a project grant from the Rebecca L Cooper Medical Research Foundation and the Maridulu Budyari Gumal Sydney Partnership for Health, Education, Research and Enterprise(SPHERE) RSEOH CAG Seed grant, fellowship and extension grant; Faculty of Health MCR/ECR Mentorship Support Grant and UTS Global Strategic Partnerships Seed Funding Scheme.

References (68)

K.S. Prabhu et al.
Sanguinarine mediated apoptosis in Non-Small Cell Lung Cancer via generation of reactive oxygen species and suppression of JAK/STAT pathway
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
(2021)
S. Jaime-Figueroa et al.
Discovery of a series of novel 5H-pyrrolo[2,3-b]pyrazine-2-phenyl ethers, as potent JAK3 kinase inhibitors
Bioorg. Med. Chem. Lett
(2013)
W. Damsky et al.
JAK inhibitors in dermatology: the promise of a new drug class
J. Am. Acad. Dermatol.
(2017)
K.S. Alharbi et al.
Nuclear factor-kappa B and its role in inflammatory lung disease
Chem. Biol. Interact.
(2021)
X. Chen et al.
Surfactant protein A modulates the activities of the JAK/STAT pathway in suppressing Th1 and Th17 polarization in murine OVA-induced allergic asthma, Laboratory investigation
J. Tech. Methods Pathol.
(2021)
S.N. Georas et al.
JAK inhibitors for asthma
J. Allergy Clin. Immunol.
(2021)
G. Karpathiou et al.
STAT6: a review of a signaling pathway implicated in various diseases with a special emphasis in its usefulness in pathology
Pathol. Res. Pract.
(2021)
D.K. Chellappan et al.
Protein and peptide delivery to lungs by using advanced targeted drug delivery
Chem. Biol. Interact.
(2022)
X. Chen et al.
Surfactant protein A modulates the activities of the JAK/STAT pathway in suppressing Th1 and Th17 polarization in murine OVA-induced allergic asthma
Lab. Invest.
(2021)
A. Alam et al.
Human gene expression profiling identifies key therapeutic targets in tuberculosis infection: a systematic network meta-analysis
Infect. Genet. Evol. : journal of molecular epidemiology and evolutionary genetics in infectious diseases
(2021)

K. Imai et al.

Mycobacterium bovis bacillus Calmette-Guérin infection promotes SOCS induction and inhibits IFN-γ-stimulated JAK/STAT signaling in J774 macrophages

FEMS Immunol. Med. Microbiol.

(2003)

J. Huang et al.

Panton-valentine leucocidin carrying Staphylococcus aureus causing necrotizing pneumonia inactivates the JAK/STAT signaling pathway and increases the expression of inflammatory cytokines

Infect. Genet. Evol.

(2020)

H. Li et al.

Feifukang ameliorates pulmonary fibrosis by inhibiting JAK-STAT signaling pathway

BMC Compl. Alternative Med.

(2018)

S. Khatiwada et al.

Lung microbiome and coronavirus disease 2019 (COVID-19): possible link and implications

Human Microbiome J.

(2020)

K.S. Alharbi et al.

Nuclear factor-kappa B and its role in inflammatory lung disease

Chem. Biol. Interact.

(2021)

L. Chen et al.

Inflammatory responses and inflammation-associated diseases in organs

Oncotarget

(2018)

F. Erdogan et al.

JAK-STAT core cancer pathway: an integrative cancer interactome analysis

J. Cell Mol. Med.

(2022)

J. Mohrherr et al.

JAK-STAT inhibition impairs K-RAS-driven lung adenocarcinoma progression

Int. J. Cancer

(2019)

M.R. Patel et al.

JAK/STAT inhibition with ruxolitinib enhances oncolytic virotherapy in non-small cell lung cancer models

Cancer Gene Ther.

(2019)

M. Shen et al.

Inhibition of ATM reverses EMT and decreases metastatic potential of cisplatin-resistant lung cancer cells through JAK/STAT3/PD-L1 pathway

J. Exp. Clin. Cancer Res. : CR

(2019)

G.Z. Sun et al.

Lung adenocarcinoma pathology stages related gene identification

Math. Biosci. Eng. : MBE

(2019)

Q. Wu et al.

JNK signaling in cancer cell survival

Med. Res. Rev.

(2019)

W. Yang et al.

LncRNA BRCAT54 inhibits the tumorigenesis of non-small cell lung cancer by binding to RPS9 to transcriptionally regulate JAK-STAT and calcium pathway genes

Carcinogenesis

(2021)

B. Cai et al.

The specific roles of JAK/STAT signaling pathway in sepsis

Inflammation

(2015)

J.J. O'Shea et al.

The JAK-STAT pathway: impact on human disease and therapeutic intervention

Annu. Rev. Med.

(2015)

X. Hu et al.

Crosstalk among Jak-STAT, Toll-like receptor, and ITAM-dependent pathways in macrophage activation

J. Leukoc. Biol.

(2007)

P. Montero et al.

Role of JAK/STAT in interstitial lung diseases; molecular and cellular mechanisms

Int. J. Mol. Sci.

(2021)

S. Banerjee et al.

JAK-STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects

Drugs

(2017)

M. Chen et al.

Inhibition of JAK-STAT signaling pathway alleviates age-related phenotypes in tendon stem/progenitor cells

Front. Cell Dev. Biol.

(2021)

F. Cordes et al.

Differential regulation of JAK/STAT-signaling in patients with ulcerative colitis and Crohn's disease

World J. Gastroenterol.

(2020)

N. Crispino et al.

JAK/STAT pathway and nociceptive cytokine signalling in rheumatoid arthritis and psoriatic arthritis

Clin. Exp. Rheumatol.

(2021)

B. Goker Bagca et al.

The potential of JAK/STAT pathway inhibition by ruxolitinib in the treatment of COVID-19

Cytokine Growth Factor Rev.

(2020)

W. Yue et al.

Exposure interval to ambient fine particulate matter (PM2.5) collected in Southwest China induced pulmonary damage through the Janus tyrosine protein kinase-2/signal transducer and activator of transcription-3 signaling pathway both in vivo and in vitro

J. Appl. Toxicol. : JAT

(2021)

K. Zhao et al.

Cigarette smoke-induced lung inflammation in COPD mediated via CCR1/JAK/STAT/NF-κB pathway

Aging

(2020)

Cited by (7)

Targeting MAPK signaling: A promising approach for treating inflammatory lung disease
2024, Pathology Research and Practice
The extracellular signals that initiate intracellular reactions are dispatched by the mitogen-activated protein kinases (MAPKs), which oversee a multitude of cellular activities. p38, Extracellular signal-regulated kinase (ERK), and c-Jun NH2-terminal kinase (JNK) are members of the vertebrate family of MAPKs, and each MAPK signaling pathway consists of a MAPK kinase (MAP3K), a MAPK kinase (MAP2K), and a MAPK. These signaling pathways orchestrate numerous cellular processes, including cell growth, survival, differentiation, and apoptosis. The emergence of various inflammatory respiratory diseases in humans has been linked to the dysregulation of MAPK signaling pathways. Conditions such as asthma, lung cancer, pulmonary fibrosis, and COPD are among the prevalent respiratory ailments where MAPK plays a pivotal role. Additionally, MAPK is implicated in infectious diseases, including COVID-19, pneumonia, and tuberculosis. COPD, asthma, emphysema, chronic bronchitis, and other inflammatory lung disorders highlight the significance of MAPK as a potential target for therapeutic development. Further studies are needed to delve into the molecular mechanisms by which the MAPK signaling pathway contributes to inflammatory lung disorders, representing an area that demands continued research.
NEAT1 in inflammatory infectious diseases: An integrated perspective on molecular modulation
2024, Pathology Research and Practice
The long non-coding RNA (lncRNA), NEAT1, has emerged as a central figure in the intricate network of molecular regulators in inflammatory infectious diseases (IIDs). The review initiates a comprehensive exploration of NEAT1's multifaceted roles and molecular interactions in the context of these complex diseases. The study begins by acknowledging the global health burden of IIDs, underscoring the urgency for innovative insights into their pathogenesis and therapeutic avenues. NEAT1 is introduced as a pivotal lncRNA with growing relevance in immune responses and inflammatory processes. The core of this review unravels the NEAT1 landscape, elucidating its involvement in the modulation of immune signalling pathways, regulation of inflammatory cytokines, and interactions with various immune cells during infection. It explores NEAT1's role in orchestrating immune responses and balancing host defence mechanisms with the risk of immunopathology. Furthermore, the review underscores the clinical significance of NEAT1 in infectious diseases, discussing its associations with disease severity, prognosis, and potential as a diagnostic and therapeutic target. It provides insights into ongoing research endeavours aimed at harnessing NEAT1 for innovative disease management strategies, including developing RNA-based therapeutics. Concluding on a forward-looking note, the review highlights the broader implications of NEAT1 in the context of emerging infectious diseases and the possibility for precision medicine approaches that leverage NEAT1's regulatory capacities. In summary, this review illuminates the pivotal role of NEAT1 in IIDs by navigating its complex landscape, offering profound insights into its implications for disease pathogenesis and the development of targeted therapies.
A comprehensive review on the emerging role of long non-coding RNAs in the regulation of NF-κB signaling in inflammatory lung diseases
2023, International Journal of Biological Macromolecules
Public health globally faces significant risks from conditions like acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and various inflammatory lung disorders. The NF-κB signaling system partially controls lung inflammation, immunological responses, and remodeling. Non-coding RNAs (lncRNAs) are crucial in regulating gene expression. They are increasingly recognized for their involvement in NF-κB signaling and the development of inflammatory lung diseases. Disruption of lncRNA-NF-κB interactions is a potential cause and resolution factor for inflammatory respiratory conditions. This study explores the therapeutic potential of targeting lncRNAs and NF-κB signaling to alleviate inflammation and restore lung function. Understanding the intricate relationship between lncRNAs and NF-κB signaling could offer novel insights into disease mechanisms and identify therapeutic targets. Regulation of lncRNAs and NF-κB signaling holds promise as an effective approach for managing inflammatory lung disorders. This review aims to comprehensively analyze the interaction between lncRNAs and the NF-κB signaling pathway in the context of inflammatory lung diseases. It investigates the functional roles of lncRNAs in modulating NF-κB activity and the resulting inflammatory responses in lung cells, focusing on molecular mechanisms involving upstream regulators, inhibitory proteins, and downstream effectors.
Uncovering the complex role of interferon-gamma in suppressing type 2 immunity to cancer
2023, Cytokine
Cancer involves cells' abnormal growth and ability to invade or metastasize to different body parts. Cancerous cells can divide uncontrollably and spread to other areas through the lymphatic or circulatory systems. Tumors form when malignant cells clump together in an uncontrolled manner. In this context, the cytokine interferon-gamma (IFN-γ) is crucial in regulating immunological responses, particularly malignancy. While IFN-γ is well-known for its potent anti-tumor effects by activating type 1 immunity, recent research has revealed its ability to suppress type 2 immunity, associated with allergy and inflammatory responses. This review aims to elucidate the intricate function of IFN-γ in inhibiting type 2 immune responses to cancer. We explore how IFN-γ influences the development and function of immune cells involved in type 2 immunity, such as mast cells, eosinophils, and T-helper 2 (Th2) cells. Additionally, we investigate the impact of IFN-mediated reduction of type 2 immunity on tumor development, metastasis, and the response to immunotherapeutic interventions. To develop successful cancer immunotherapies, it is crucial to comprehend the complex interplay between type 2 and type 1 immune response and the regulatory role of IFN-γ. This understanding holds tremendous promise for the development of innovative treatment approaches that harness the abilities of both immune response types to combat cancer. However, unraveling the intricate interplay between IFN-γ and type 2 immunity in the tumor microenvironment will be essential for achieving this goal.
Identification of Related-Genes of T cells in Lung Tissue of Chronic Obstructive Pulmonary Disease Based on Bioinformatics and Experimental Validation
2024, Research Square
Methylomic, Proteomic, and Metabolomic Correlates of Traffic-Related Air Pollution in the Context of Cardiorespiratory Health: A Systematic Review, Pathway Analysis, and Network Analysis
2023, Toxics

View all citing articles on Scopus

View full text

Review ArticleJanus kinase/signal transducers and activator of transcription (JAK/STAT) and its role in Lung inflammatory disease

Highlights

Abstract

Introduction

Section snippets

History of JAK/STAT

Lung inflammatory disease and JAK/STAT

Conclusion and future prospective

Declaration of competing interest

Acknowledgement

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Bioorg. Med. Chem. Lett

J. Am. Acad. Dermatol.

Chem. Biol. Interact.

J. Tech. Methods Pathol.

J. Allergy Clin. Immunol.

Pathol. Res. Pract.

Chem. Biol. Interact.

Lab. Invest.

Infect. Genet. Evol. : journal of molecular epidemiology and evolutionary genetics in infectious diseases

FEMS Immunol. Med. Microbiol.

Infect. Genet. Evol.

BMC Compl. Alternative Med.

Human Microbiome J.

Chem. Biol. Interact.

Inflammatory responses and inflammation-associated diseases in organs

Oncotarget

JAK-STAT core cancer pathway: an integrative cancer interactome analysis

J. Cell Mol. Med.

JAK-STAT inhibition impairs K-RAS-driven lung adenocarcinoma progression

Int. J. Cancer

JAK/STAT inhibition with ruxolitinib enhances oncolytic virotherapy in non-small cell lung cancer models

Cancer Gene Ther.

Inhibition of ATM reverses EMT and decreases metastatic potential of cisplatin-resistant lung cancer cells through JAK/STAT3/PD-L1 pathway

J. Exp. Clin. Cancer Res. : CR

Lung adenocarcinoma pathology stages related gene identification

Math. Biosci. Eng. : MBE

JNK signaling in cancer cell survival

Med. Res. Rev.

LncRNA BRCAT54 inhibits the tumorigenesis of non-small cell lung cancer by binding to RPS9 to transcriptionally regulate JAK-STAT and calcium pathway genes

Carcinogenesis

The specific roles of JAK/STAT signaling pathway in sepsis

Inflammation

The JAK-STAT pathway: impact on human disease and therapeutic intervention

Annu. Rev. Med.

Crosstalk among Jak-STAT, Toll-like receptor, and ITAM-dependent pathways in macrophage activation

J. Leukoc. Biol.

Role of JAK/STAT in interstitial lung diseases; molecular and cellular mechanisms

Int. J. Mol. Sci.

JAK-STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects

Drugs

Inhibition of JAK-STAT signaling pathway alleviates age-related phenotypes in tendon stem/progenitor cells

Front. Cell Dev. Biol.

Differential regulation of JAK/STAT-signaling in patients with ulcerative colitis and Crohn's disease

World J. Gastroenterol.

JAK/STAT pathway and nociceptive cytokine signalling in rheumatoid arthritis and psoriatic arthritis

Clin. Exp. Rheumatol.

The potential of JAK/STAT pathway inhibition by ruxolitinib in the treatment of COVID-19

Cytokine Growth Factor Rev.

Exposure interval to ambient fine particulate matter (PM2.5) collected in Southwest China induced pulmonary damage through the Janus tyrosine protein kinase-2/signal transducer and activator of transcription-3 signaling pathway both in vivo and in vitro

J. Appl. Toxicol. : JAT

Cigarette smoke-induced lung inflammation in COPD mediated via CCR1/JAK/STAT/NF-κB pathway

Aging

Review Article
Janus kinase/signal transducers and activator of transcription (JAK/STAT) and its role in Lung inflammatory disease