Increase of activated T-cells and up-regulation of Smad7 without elevation of TGF-beta expression in tonsils from patients with pustulosis palmaris et plantaris

Takahara, Miki; Kishibe, Kan; Nozawa, Hayabusa; Harabuchi, Yasuaki

doi:10.1016/j.clim.2005.01.001

Cited by 25 publications

(23 citation statements)

References 46 publications

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“…Recent studies have demonstrated that Smad7 expression is induced by TGF-b, EGF and the inflammatory cytokines, such as TNF-a and IFN-g (Afrakhte et al, 1998;Takahara et al, 2005). Upregulation of Smad7 may induce cell proliferation through the inhibition of p21…”

Section: Discussionmentioning

confidence: 99%

Smad7 induces hepatic metastasis in colorectal cancer

et al. 2008

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Although Smad signalling is known to play a tumour suppressor role, it has been shown to play a prometastatic function also in breast cancer and melanoma metastasis to bone. In contrast, mutation or reduced level of Smad4 in colorectal cancer is directly correlated to poor survival and increased metastasis. However, the functional role of Smad signalling in metastasis of colorectal cancer has not been elucidated. We previously reported that overexpression of Smad7 in colon adenocarcinoma (FET) cells induces tumorigenicity by blocking TGF-b-induced growth inhibition and apoptosis. Here, we have observed that abrogation of Smad signalling by Smad7 induces liver metastasis in a splenic injection model. Polymerase chain reaction with genomic DNA from liver metastases indicates that cells expressing Smad7 migrated to the liver. Increased expression of TGF-b type II receptor in liver metastases is associated with phosphorylation and nuclear accumulation of Smad2. Immunohistochemical analyses have suggested poorly differentiated spindle cell morphology and higher cell proliferation in Smad7-induced liver metastases. Interestingly, we have observed increased expression and junctional staining of Claudin-1, Claudin-4 and E-cadherin in liver metastases. Therefore, this report demonstrates, for the first time, that blockade of TGF-b/Smad pathway in colon cancer cells induces metastasis, thus supporting an important role of Smad signalling in inhibiting colon cancer metastasis. Metastasis is the major cause of cancer morbidity and mortality, and accounts for 90% of cancer deaths. Despite the fact that metastasis ultimately kills the host, the mechanisms leading to tumour invasion and metastasis have been less characterized than those resulting in tumour initiation. Cancer development and metastasis is a multistep process that involves local tumour growth and invasion followed by dissemination to, and re-establishment at, the distant sites (Liotta et al, 1991;Oft et al, 2002). There is compelling evidence indicating that TGF-b has complex roles in tumour suppression and progression that are context-and stagedependent. Therefore, elucidating the molecular pathways essential for tumour metastasis is a higher priority in the pathobiology of cancer to design small molecule drugs.Family members of TGF-b initiate signalling from the cell surface by binding to a heteromeric complex of two distinct but related serine/threonine kinase receptors. Binding of the ligand to the type II receptor (TbRII) results in recruitment and phosphorylation of the type I receptor (TbRI).

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Section: Discussionmentioning

confidence: 99%

Smad7 induces hepatic metastasis in colorectal cancer

et al. 2008

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“…Takahara et al published a case series reporting an improvement in skin lesions in 87% of PPP patients (n = 47) at 12 months following tonsillectomy (10) (Table 1). The group then reported a prospective case series of 116 patients undergoing tonsillectomy for the treatment of PPP (11).…”

Section: Resultsmentioning

confidence: 99%

Tonsillectomy as a treatment for psoriasis: A review

Debbaneh

Moslehi

et al. 2013

Journal of Dermatological Treatment

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Psoriasis is a chronic skin disorder that affects 1% to 3% of the general population worldwide. Streptococcal infection, especially streptococcal pharyngitis, has been shown to be a significant trigger of psoriasis in some patients, possibly by sensitizing T cells to keratin epitopes in the skin. Due to the role of the palatine tonsils as an immunological organ that may generate autoreactive T cells, tonsillectomy has been investigated as a treatment for psoriasis. Tonsillectomy originally gained acceptance in Japan as a treatment for palmoplantar pustulosis, a condition that shares features with pustular psoriasis. Subsequently, tonsillectomy has been used for the treatment of plaque psoriasis and guttate psoriasis. Recently, the first randomized, controlled clinical trial of tonsillectomy was performed. Here, we review the available evidence for the benefit of tonsillectomy as a treatment for palmoplantar pustulosis and psoriasis. We also discuss molecular studies aimed at understanding the role of tonsils in skin disease.

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“…Tonsillar T cells in PPP patients were supposed to exhibit higher levels of activity and proliferation. We determined through quantitative immunohistological analysis that T‐cell nodules on tonsillar tissues of PPP patients were more expanded; additionally, there was a positive correlation between the enlargement and clinical improvement of skin lesions after tonsillectomy. Kawaguchi et al .…”

Section: Pathogenic Role Of Tonsils In Pppmentioning

confidence: 99%

Pathogenic role of palatine tonsils in palmoplantar pustulosis: A review

Harabuchi

Takahara

2019

The Journal of Dermatology

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Palmoplantar pustulosis (PPP) is characterized by symmetrical, erythematous, scaly plaques, with numerous, sterile, non‐bacterial, pinpoint pustules, which are restricted to the palms and soles. Because several reports have described the efficacy of tonsillectomy for improvement in PPP skin lesions, we consider that PPP is tonsil‐induced autoimmune/inflammatory syndrome (TIAS) while other factors are also involved in the pathogenesis of PPP. Here, the association between PPP pathogenesis and TIAS was examined, with a focus on results of previous studies. PPP patients show a hyperimmune response to indigenous bacteria such as α‐streptococci, due to impaired immunological tolerance towards such organisms. Such a novel immune response leads to T‐cell activation through the abnormal expression of secondary stimulation molecules, including cytotoxic T‐lymphocyte‐associated antigen 4, inducible T‐cell co‐stimulator and Smad7, in the tonsils of PPP patients. Activated tonsillar T cells express cutaneous lymphocyte antigen (CLA), CCR6 and β1‐integrin, enter the blood circulation and are recruited to PPP skin lesions. Within lesions, T cells roll onto endothelial cells through the interaction between CLA and E‐selectin, migrate into the extravascular area through β1‐integrin–vascular cell adhesion molecule 1 binding, and assemble in the skin through CCL20–CCR6 binding. Hyperimmune responses to autoantigens such as keratin and heat shock proteins could also be involved in PPP pathogenesis, through the stimulation of the T‐helper 17 reaction.

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Increase of activated T-cells and up-regulation of Smad7 without elevation of TGF-beta expression in tonsils from patients with pustulosis palmaris et plantaris

Cited by 25 publications

References 46 publications

Smad7 induces hepatic metastasis in colorectal cancer

Smad7 induces hepatic metastasis in colorectal cancer

Tonsillectomy as a treatment for psoriasis: A review

Pathogenic role of palatine tonsils in palmoplantar pustulosis: A review

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