Jak-Stat signaling pathway may play a role in the pathogenesis of cholesteatoma

Eskıızmır, Görkem; Vatansever, Hafize Seda; Özgür, Erdogan; Aslan, Asım; Tanyeri, Gökçe; Gözüaçık, Derya; Özbilgin, Mahmut Kemal; Cingi, Cemal

doi:10.1016/j.amjoto.2013.10.005

Cited by 4 publications

(4 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Only a few studies have previously showed interest in the JAK/STAT pathway in cholesteatomas. Downregulation of JAK1, JAK2 and JAK3, and STAT1, STAT2, STAT4 and STAT5 in cholesteatoma matrix (Eskiizmir et al 2014) and increased expression of STAT3 and IL-6 in cholesteatomas have previously been reported (Liu et al 2014). In these immunohistochemical studies, the cholesteatoma matrix was investigated with the skin from the ear canal as control.…”

Section: Nitric Oxide and Nitric Oxide Synthasementioning

confidence: 84%

“…STAT5 is expressed in most cell types and activated by a variety of cytokines, each with a defined function (Ihle 1996). The potential involvement of the JAK/STAT pathway in the pathogenesis in cholesteatoma has been investigated in earlier publications, but it is still largely unknown, and conflicting results have been found (Eskiizmir et al 2014, Liu et al 2014). An overexpression of STAT3 (Liu et al 2014), in contrast to a deficiency in JAK/STAT signalling (Eskiizmir et al 2014), was found in cholesteatoma matrix compared to skin from the ear canal.…”

Section: Janus Kinase/signal Transducer and Activator Of Transcriptiomentioning

confidence: 99%

See 1 more Smart Citation

Middle ear cholesteatoma : Surgical outcome and aspects of the innate immunity

Westerberg

2020

Linköping University Medical Dissertations

View full text Add to dashboard Cite

Cholesteatomas are bone destructive expansions of keratinizing squamous epithelium in the middle ear and temporal bone. Today, surgery is the only treatment. There are several controversies regarding cholesteatomas, including the definition, the pathogenesis and the surgical method. Intense efforts have been made searching for a comprehension of the cholesteatoma process at a cellular and molecular level. Recurrent infections and inflammation seem to be contributing factors for the cholesteatomas to expand. The innate immunity, essential to keep a healthy middle ear environment and to protect the middle ear from intruding pathogens, is therefore a matter of interest. In this thesis, results are presented from a cohort of cholesteatoma surgeries in Östergötland from a 16-year period. A group of patients also filled in a questionnaire to assess changes in health-related quality of life (HRQoL) after surgery. According to the findings in this thesis, the residual and recurrence frequencies are low, and the hearing and HRQoL are improved in the majority of cases. This thesis also presents an investigation of the innate immunity in ears with acquired cholesteatoma, in comparison to controls with healthy middle ears. The expression of mRNA of toll like receptors 2 and 4, participants of the Janus kinase/signal transducer and activator of transcription pathway, and nitric oxide synthases in middle ear mucosa, were investigated with quantitative polymerase chain reaction. An investigation of nitric oxide (NO) in the middle ear, with chemiluminescence measurements, is also presented. A derangement of the innate immune system is seen in ears with cholesteatoma, which supports the idea that the innate immunity participates in the cholesteatoma process, though the underlying mechanisms are still unclear. The suggestion of NO production in the middle ear sheds light on NOs possible participation in the healthy middle ear environment.

show abstract

Section: Nitric Oxide and Nitric Oxide Synthasementioning

confidence: 84%

Section: Janus Kinase/signal Transducer and Activator Of Transcriptiomentioning

confidence: 99%

Middle ear cholesteatoma : Surgical outcome and aspects of the innate immunity

Westerberg

2020

Linköping University Medical Dissertations

View full text Add to dashboard Cite

show abstract

“…The human JAK3 gene is predominantly expressed in lymphoid and myeloid cells and located in chromosome 19p12-13.1, consisting of 23 exons and an open reading frame of 3,372 nucleotides ( 1 , 2 , 14 – 17 ). Tyrosine kinase JAK3 binds specially to the γ c subunit, an essential component of the cytokine (i.e., IL-2, IL-4, IL-7, IL-9, IL-10, IL-11, IL-15, and IL-21) receptor complexes ( Figure 2 ) ( 1 , 7 , 15 , 18 ). Intracellular activation signal through cytokine-γ c - JAK3 binding induces JAK3 to phosphorylate signal transducer and activator of transcription (STAT) proteins (i.e., STAT1, STAT3, STAT5, and STAT6) ( 18 , 19 ), which therefore dimerize and translocate to the nucleus to initiate the transcription program ( 1 , 7 ).…”

Section: Discussionmentioning

confidence: 99%

“…Tyrosine kinase JAK3 binds specially to the γ c subunit, an essential component of the cytokine (i.e., IL-2, IL-4, IL-7, IL-9, IL-10, IL-11, IL-15, and IL-21) receptor complexes ( Figure 2 ) ( 1 , 7 , 15 , 18 ). Intracellular activation signal through cytokine-γ c - JAK3 binding induces JAK3 to phosphorylate signal transducer and activator of transcription (STAT) proteins (i.e., STAT1, STAT3, STAT5, and STAT6) ( 18 , 19 ), which therefore dimerize and translocate to the nucleus to initiate the transcription program ( 1 , 7 ). While IL-2, IL-4, and IL-9 play crucial roles in the development of B cells and T cells ( 1 , 14 , 20 ), IL-7 and IL-15 mainly regulate the differentiation and activation of T cells and NK cells ( 1 , 2 , 6 , 14 , 21 ).…”

Section: Discussionmentioning

confidence: 99%

Case Report: Mutations in JAK3 causing severe combined immunodeficiency complicated by disseminated Bacille Calmette–Guérin disease and Pneumocystis pneumonia

et al. 2022

View full text Add to dashboard Cite

BackgroundAs a form of severe combined immunodeficiency (SCID), Janus kinase 3 (JAK3) deficiency can be fatal during severe infections in children, especially after inoculation of live-attenuated vaccines. We report a unique case of JAK3 deficiency with two compound heterozygous JAK3 mutations complicated by disseminated Bacille Calmette–Guérin (BCG) disease and Pneumocystis pneumonia.Case descriptionA 5-month-old Chinese girl presented with recurring fever and productive cough after BCG vaccination and ineffective antibiotic treatment. Chest CT demonstrated bilateral infiltrations, enlarged mediastinal and axillary lymph nodes, and hypoplasia of the thymus. Mycobacterium tuberculosis and Pneumocystis jirovecii were detected from blood samples by sequencing. Acid-fast bacilli were also found from the sputum aspirate and gastric aspirate. Lymphocyte subset analyses indicated T-B+NK- immunodeficiency, and gene sequencing identified two heterozygous missense mutations (one unreported globally) in the Janus homology 7 (JH7) domain of JAK3. The patient received rifampicin, isoniazid, ethambutol, and trimethoprim/sulfamethoxazole and was discharged after improvements but against advice.OutcomeThe patient died at 13 months of age due to severe infections and hepatic damage.DiscussionSCID should be recognized before inoculation of live-attenuated vaccines in children. Newborn screening for SCID is advocated. Further investigations are needed to better understand the pathogenicity of the variants and molecular mechanism of the JH7 domain of JAK3.

show abstract

Modulation of apoptosis-related cell signalling pathways by curcumin as a strategy to inhibit tumor progression

2014

View full text Add to dashboard Cite

A hallmark of cancer is resistance to apoptosis, with both the loss of proapoptotic signals and the gain of anti-apoptotic mechanisms contributing to tumorigenesis. As inducing apoptosis in malignant cells is one of the most challenging tasks regarding cancer, researchers increasingly focus on natural products to regulate apoptotic signaling pathways. Curcumin, a polyphenolic derivative of turmeric, is a natural compound derived from Curcuma longa, has attracted great interest in the research of cancer during the last half century. Extensive studies revealed that curcumin has chemopreventive properties, which are mainly due to its ability to arrest cell cycle and to induce apoptosis in cancer cells either alone or in combination with chemotherapeutic agents or radiation. The underlying action mechanisms of curcumin are diverse and has not been elucidated so far. By regulating multiple important cellular signalling pathways including NF-κB, TRAIL, PI3 K/Akt, JAK/STAT, Notch-1, JNK, etc., curcumin are known to activate cell death signals and induce apoptosis in pre-cancerous or cancer cells without affecting normal cells, thereby inhibiting tumor progression. Several phase I and phase II clinical trials indicate that curcumin is quite safe and may exhibit therapeutic efficacy. This article reviews the main effects of curcumin on the different apoptotic signaling pathways involved in curcumin induced apoptosis in cancer cells via cellular transduction pathways and provides an in depth assessment of its pharmacological activity in the management of tumor progression.

show abstract

Jak-Stat signaling pathway may play a role in the pathogenesis of cholesteatoma

Cited by 4 publications

References 32 publications

Middle ear cholesteatoma : Surgical outcome and aspects of the innate immunity

Middle ear cholesteatoma : Surgical outcome and aspects of the innate immunity

Case Report: Mutations in JAK3 causing severe combined immunodeficiency complicated by disseminated Bacille Calmette–Guérin disease and Pneumocystis pneumonia

Modulation of apoptosis-related cell signalling pathways by curcumin as a strategy to inhibit tumor progression

Contact Info

Product

Resources

About