Search

Invasion of antigens through the mucosal surface can be prevented by the common mucosal immune system, including Peyer's patches (PPs) and nasopharyngeal-associated lymphoreticular tissue (NALT). The adenoids (nasopharyngeal tonsils) comprise one of the NALTs and constitute the major part of Waldeyer's lymphoid ring in humans. However, the role of the lymphoepithelium, including M cells and dendritic cells (DCs), in the adenoids is unknown compared with the epithelium of PPs. NALTs also have unique functions such as the barrier of epithelial cells and uptake of antigens by M cells and DCs, and may play a crucial role in airway mucosal immune responses. The lymphoepithelium of adenoids has well-developed tight junctions that play an important role in the barrier function, the same as nasal epithelium but not palatine tonsillar epithelium. Tight junction molecules are expressed in both M cells and DCs as well as epithelial cells, and various antigens may be sampled, transported, and released to lymphocytes through the cells while they maintain the integrity of the epithelial barrier. This review summarizes the recent progress in our understanding of how M cells and DCs control the epithelial barrier in the adenoids. [ABSTRACT FROM AUTHOR]

Abstract: Gap junctions are considered to play a crucial role in differentiation of epithelial cells and to be associated with tight junction proteins. In this study, to investigate the role of gap junctions in regulation of the barrier function and fence function on the tight junctions, we introduced the Cx26 gene into human airway epithelial cell line Clau-3 and used a disruption model of tight junctions employing the Na+/K+-ATPase inhibitor ouabain. In parental Calu-3 cells, gap junction proteins Cx32 and Cx43, but not Cx26, and tight junction proteins occludin, JAM-1, ZO-1, claudin-1, -2, -3, -4, -5, -6, -7, -8, -9, and -14 were detected by RT-PCR. The barrier function and fence function of tight junctions were well maintained, whereas the GJIC was low level. Treatment with ouabain caused disruption of the barrier function and fence function of tight junctions together with down-regulation of occludin, JAM-1, claudin-2, and -4 and up-regulation of ZO-1 and claudin-14. In Cx26 transfectants, Cx26 protein was detected by Western blotting and immunocytochemistry, and many gap junction plaques were observed with well-developed tight junction strands. Expression of claudin-14 was significantly increased in Cx26 transfectants compared to parental cells, and in some cells, Cx26 was co-localized with claudin-14. Interestingly, transfection with Cx26 prevented disruption of both functions of tight junctions by treatment with ouabain without changes in the tight junction proteins. Pretreatment with the GJIC blockers 18β-glycyrrhetinic acid and oleamide did not affect the changes induced by Cx26 transfection. These results suggest that Cx26 expression, but not the mediated intercellular communication, may regulate tight junction barrier and fence functions in human airway epithelial cell line Calu-3. [Copyright &y& Elsevier]

Rho-kinase inhibitor Y27632, which is a factor in conditional reprogramming culture, induces airway progenitor clone formation. To investigate whether Y27632 enhances airway progenitor cells in nasal epithelium, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were treated with Y27632. In TERT-HNECs treated with Y27632 for 5 days, upregulation of p63, gap junction molecules Cx26, Cx30, Cx43, cytochrome P450 enzymes CYP2C9, CYP2C18, CYP39A1, CYP4B1, CYP2G1P, CYP4Z1, and KLF families KLF10 and KLF11 were observed compared to the control. Downregulation of tight junction molecules claudin-4, -7, and -23 was observed. Circumfential submembrane F-actin was also induced. The functions of gap junctional intercellular communication (GJIC) and the epithelial barrier were upregulated. Knockdown of p63 by siRNAs of TAp63 or ΔNp63 inhibited Cx26, Cx43 and CYP2C18, and induced claudin-1, and -4. Knockdown of KLF11 prevented p63 expression and enhancement of the epithelial barrier function by Y27632. In nasal mucosal tissues from patients with allergic rhinitis (AR), localized alteration of p63, KLF11, RhoA, Cx30 and claudin-4 was observed. Treatment with Y27632 in long-term culture induced airway progenitor cells via KLF11 in p63-positive human nasal epithelium. Airway progenitor cells of nasal epithelium induced by Y27632 is important in understanding upper airway disease-specific characteristics., Competing Interests: None.

Background/aim: To analyze the clinical features and prevalence of synchronous and metachronous second primary malignancies (SPMs) in patients with hypopharyngeal squamous cell carcinoma (HSCC), their associated risk factors, and cause-specific mortality., Patients and Methods: We retrospectively reviewed 136 patients treated with curative intent at our hospital. Statistical analyses were performed to determine factors predictive of SPM and cause-specific mortality., Results: Sixty-three of 136 patients (46.3%) developed SPM; of these, 41 (30.1%) and 42 (30.9%) had synchronous and metachronous SPMs, respectively, with patient overlap. The most common site of synchronous and metachronous SPMs was the oesophagus (65.8% and 24.4%, respectively); the corresponding overall survival rates were 34.1% and 66.5%, respectively. Furthermore, heavy drinking was significantly correlated with synchronous SPM (p<0.001)., Conclusion: Oesophageal cancer surveillance is recommended for patients with HSCC, especially heavy drinkers. Our findings may help identify and properly manage HSCC patients at high risk of SPMs., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Junctional adhesion molecule-A (JAM-A), which belongs to the IgG superfamily, is one of the tight junction molecules. JAM-A is dysregulated in various cancers and is closely associated with the invasion and metastasis of cancers such as breast cancer, lung cancer and pancreatic cancer. In the present study, we found a high expression of JAM-A in head and neck squamous cell carcinoma (HNSCC) as well as β-catenin in immunohistochemistry. The expression of JAM-A and β-catenin was of a low level in differentiation-induced cancer pearl regions of HNSCC. Real-time PCR showed the high expression of JAM-A mRNA through all differentiated stages (well, moderate, poor) of HNSCC. When we performed ELISA using the serum of HNSCC patients to measure plasma-soluble JAM-A, it was found to be higher in HNSCC patients than healthy subjects. These results indicate that JAM-A is one of the malignancy markers of HNSCC as well as β-catenin in histopathology, and the plasma-soluble JAM-A may contribute to a serum diagnosis of HNSCC. JAM-A is a promising molecular target for diagnosis and therapy in HNSCC., (© 2016 S. Karger AG, Basel.)

Inflammasomes, large protein complexes typically consisting of a Nod-like receptor (NLR), adapter protein apoptosis-associated speck-like protein containing CARD (ASC) and caspase-1, are postulated to be activated in response to danger signals arising from tumors. Inflammasomes are thought to have critical but contrasting roles through facilitating antitumor immunity and inducing oncogenic factors. However, the role and function of inflammasomes in oropharyngeal carcinoma remain unclear. We analyzed nine specimens of oropharyngeal squamous cell carcinoma (SCC) and determined the expression of NLRP3, ASC, interleukin (IL)-1β, IL-18 and caspase-1 in the specimens with and without human papilloma virus (HPV) infection using immunohistochemistry, and analyzed the correlations between the altered expression of these proteins and clinicopathological factors of oropharyngeal SCC. We found strong expression of NLRP3, ASC, IL-1β, IL-18 and caspase-1 in human oropharyngeal SCC and weak or no expression of these proteins in normal tonsils. Furthermore, the distribution of mindbomb E3 ubiquitin protein ligase 1 and inflammasome-associated proteins in oropharyngeal SCC was not significantly different; there was no correlation between the expression of inflammasome-associated proteins and HPV infection. These findings suggest that inflammasomes in oropharyngeal SCC play a key role through facilitating antitumor immunity and the possibility of new roles for inflammasomes in the oropharynx., (© 2016 S. Karger AG, Basel.)

Purpose: We investigated seasonal allergic conjunctivitis in Hakodate., Materials and Methods: The clinical records of 293 patients with allergy-like symptoms who were seen at the Departments of Ophthalmology and Otolaryngology of Hakodate Municipal Hospital in 2001 and 2002 were examined for pollinosis, and evaluated. The general severity of conjunctivitis was graded as (+), (++), and (+++). The allergen was identified by AlaSTAT and nasal provocation test., Results: In March, June, and September 2001, and in March, April, and June 2002, many patients were examined. In 2001, 134 patients (87.0%) had allergic conjunctivitis, and 126 patients (90.6%) had it in 2002. The severity of allergic conjunctivitis in May, June, and September was significantly (p<0.05) more severe than in February, March, and April. The major antigen rates for Cryptomeria japonica, Gramineae, Artemisia, and Betula platyphyia var. japonica were 22, 21, 8, and 3%. The specific IgE positive rates for Cryptomeria japonica, Betula platyphyia var. japonica, Gramineae and Artemisia were higher in March and April, in May, in June, and in September., Conclusion: The allergens of conjunctivitis in Hakodate were not the same as in the Kansai. We should consider the dispersion of pollens area by area.

We have investigated the nasal and eye symptoms of pollinosis in Hakodate. There were elevated levels of dispersion of Cryptomeria japonica pollen in Hakodate in 1995 and 1998. In 1995 and 2001, there were also elevated levels of dispersion of Betula platyphylia var. japonica pollen. From March to June and September from July 1999 to May 2002, there was an increased incidence of pollinosis in Hakodate. In 641 patients with allergic rhinitis, the specific IgE positive rates for house dust and mite, Artemisia (Art), Gramineae (Gra), Betulaplatyphylia var. japonica (BJ), and Cryptomeria Japonica (CJ) were 73.5, 28.5, 25.7, 14.2 and 21.2%, respectively. The subjects with pollinosis in 2001 and 2002 (n=95) were divided into four groups as follows: Cryptomeria japonica (n=49), Betula platyphylia var. japonica (n=11), Gramineae (n=18) and Artemisia (n=17) pollinosis. The general severity of rhinitis and conjunctivitis were divided into four grades ( (-), (+), (++) and (+++) ), respectively. The combined (++) and (+++) rates observed for the general severity of rhinitis for all these subjects (n=95) was 86.4% and there was no significant difference in the general severity of rhinitis between any of the four groups. The combined (++) and (+++) rates for the general severity of conjunctivitis for all subjects (n=95) was 56.9% and the general severity of conjunctivitis for BJ and Gra pollinosis were significantly (P<0.01) higher than those observed for CJ pollinosis. In conclusion, the present data shows that the general severity of rhinitis in subjects with pollinosis in Hakodate was more severe than that of conjunctivitis and also that the general severity of conjunctivitis was dependent on the specific pollen (s) responsible for the pollinosis.