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ORIGINAL ARTICLE Table of Contents   
Year : 2010  |  Volume : 53  |  Issue : 3  |  Page : 451-454
Expression of cyclooxygenase-1 and 2 in chronic tonsillitis

1 Department of Pathology and Ear, Nose, Kocatepe University, School of Medicine, Afyonkarahisar, Turkey
2 Department of Throat, Kocatepe University, School of Medicine, Afyonkarahisar, Turkey

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Date of Web Publication22-Oct-2010


Objectives: Prostaglandins are critical mediators of inflammation and affect both humoral and cell-mediated immune responses. Recent findings show that T and B cells express COX-2 upon activation. The purpose of this study is to investigate the potential occurrence of COX-1 and COX-2 immunoreactivity in cases of chronic tonsillitis and to determine the sites of their expression. In addition, their expression in adult patients is compared with that in child patients. Materials and Methods: Immunohistochemical techniques were used to evaluate the expression of the enzymes COX-1 and COX-2, in chronic tonsillitis tissue specimens from adults (n = 15) and children (n = 15). Results: There was no staining in surface epithelium or reticulated crypt epithelium. COX-1 and COX-2 expressions were observed mainly in the intraepithelial lymphoid cells in reticulated crypt epithelium and subepithelial cells. Also, COX-1 and COX-2 stained cells were found in the germinal center. There was no difference of the expressions of COX-1 and COX-2 among adults and children. The only significant difference noted between the adults and children was that, the adults had rich subepithelial plasma cells. Conclusion: Activated B and T cells express COX-1 and COX-2 in paraffin-embedded tissue sections of chronic tonsillitis. Further studies need to be performed to elucidate expression of COX enzymes and their immunologic role in tonsil diseases. They will play an important role in the treatment of chronic tonsillitis. Additional studies are warranted to study the effects of NSAIDs and selective COX-2 inhibitors in chronic tonsillitis

Keywords: Cyclooxygenase-1, cyclooxygenase-2, tonsillitis

How to cite this article:
Dilek FH, Sahin O, Tokyol C, Mazlum M, Aycicek A. Expression of cyclooxygenase-1 and 2 in chronic tonsillitis. Indian J Pathol Microbiol 2010;53:451-4

How to cite this URL:
Dilek FH, Sahin O, Tokyol C, Mazlum M, Aycicek A. Expression of cyclooxygenase-1 and 2 in chronic tonsillitis. Indian J Pathol Microbiol [serial online] 2010 [cited 2022 Jul 3];53:451-4. Available from: https://www.ijpmonline.org/text.asp?2010/53/3/451/68272

   Introduction Top

The palatine tonsils are a part of the circular band of pharyngeal lymphoid tissue surrounding the openings into the digestive and respiratory tracts, and lie in a position critical for immunological surveillance of airborne and orally presented antigens. The epithelium overlying the lymphoid follicles of the palatine tonsils is closely adapted to suit this function as inhaled and ingested microorganisms must transverse it before they can initiate immune reactions to protect the body. [1],[2]

Cyclooxygenase (COX) also referred to as prostaglandin (PG) endoperoxide, catalyze a Cox (bis-oxygenase) reaction in which arachidonic acid is converted to PGG2, and a subsequent peroxidase reaction in which PGG2 undergoes a two-electron reduction to PGH2, the common precursor to all prostanoids, including PGE2, PGD2, PGF2, PGI2, and thromboxane. Prostaglandins are critical mediators of inflammation. Two COX isoforms, COX-1 and COX-2, have been identified. COX-1 (constitutive type) is present in most cells and tissues, supporting eicosanoid synthesis required for tissue homeostasis, and an inducible isoenzyme (COX-2) is expressed in response to cytokines, growth factors, and stressors such as hypoxia and free radicals. [3],[4]

The purpose of this study was to investigate the potential occurrence of COX-1 and COX-2 immunoreactivity in cases of chronic tonsillitis and to determine the sites of their expression. In addition, COX-1 and COX-2 expression was compared in adults and children. To the best of our knowledge, this is the first report describing of COX expression in chronic tonsillitis.

   Materials and Methods Top

The study subjects included patients diagnosed with chronic tonsillitis and also advised to undergo tonsillectomy. This study was reviewed and approved by the institutional review board. The patients were grouped according to age. The group with adults consisted of 15 patients, with a mean age of 20 years (range 18-35). The group of children consisted of 15 patients, with a mean age of eight years (range 3-10). Thirty paraffin sections belonging to these patients were examined.

Immunohistochemical studies were performed using the avidin-biotin technique. The reaction products were visualized with aminoethylcarbazol (AEC) as chromogene and the sections were counterstained with Mayer's hematoxylin. Monoclonal antibodies COX-1 (NCL-COX-1, Novocastra, UK, dilution: 1: 30) and COX-2 (Neomarkers, LabVision Coop, CA, USA, dilution 1:150) were used. A heat-induced epitope retrieval method with microwave oven was employed prior to the immunostaining. The sections were incubated with the primary antibodies; one hour at 37ΊC for COX-1 and 30 minutes at room temperature for COX-2.

Assessment of COX-1 and COX-2 immunoreactivity was performed according to number of positive cytoplasmic staining. For two antibodies, three areas with the highest density of positive cells were selected at Χ100 magnification. The positive stained cells in both germinal center and interfollicular area were counted in three high-power fields (Χ400), by an image analysis system (BS200Docu Version 2.0; BAB Imaging Systems, Ankara, Turkey) and their median number was recorded.

Statistical analysis was performed using the SPSS 13.0 software. The results were expressed as mean values ± SD. The Mann-Witney -U test was employed for two-group comparison. Two-tailed P value < 0.05 was considered to be statistically significant.

   Results Top

Follicular hyperplasia and enlargement of follicles were prominent in tonsil tissues of children. We observed that some cases had rich plasma cell in subepithelial area of surface epithelium. Thus, we noted nine cases in the adult group and two cases in children group. It was significant statistically (P = 0.021).

Immunoreactivity of COX-1 and COX-2 was observed in lymphoid cells at tonsil tissue. Neither COX-1, nor COX-2 were detectable in the squamous epithelium or reticulated crypt epithelium. Lymphocytes in the mantle zone were not staining for two antibodies.

COX-1 expression was detected in some cells that were macrophages in germinal centers. Those cells had abundant cytoplasm and some contained ingested material (tingible body macrophage) [Figure 1]a. Subepithelial plasma cells [Figure 1]b, intraepithelial lymphocytes [Figure 1]c exhibited expression of COX-1 antibody. Further, specialized venules, the so-called high-endothelial venules showed COX-1 immunoreactivity.
Figure 1 :Immunoreactivity to COX-1 in chronic tonsillitis; (a) macrophages in germinal center (×1000), (b) subepithelial cells (×200), (c) intraepithelial lymphoid cells in lymphoepithelium (×200).

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Similar to COX-1 immunoreactivity, COX-2 expression was observed in the subepithelial lymphocytes and plasma cells [Figure 2]a and intraepithelial lymphocytes [Figure 2]b. Some cells in germinal center showed COX-2 expression, those cells were like centrocytes or centroblast, have vesicular, cleaved or non-cleaved nuclei and a greater amount of cytoplasm than the lymphocyte [Figure 2]c. In addition, COX-2 expression was observed some lymphoid cells in interfollicular areas.
Figure 2 :COX-2 positi ve cells in chronic tonsilliti s; (a) subepithelial cells (×400), (b) lymphoid cells in crypt epithelium (×200) (c) Centrocyte or centroblast like cells in germinal center (×1000).

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The number of COX-2 and COX-1 immunoreactivated germinal center cells were 6.76 ± 3.44, 17.65 ± 13.26 in adults and

7.56 ± 4.59, 23.46 ± 9.43 in children, respectively. The number of COX-1 and COX-2 positive cell in tonsils of children was larger than adults, but it was not different statistically (P > 0.05).

   Discussion Top

COX-1 and COX-2 are important enzymes that mediate inflammatory processes. COX-2 is the predominant isoform contributing to high levels of PGE2 found in chronic inflammatory conditions. [3],[4],[5] On the other hand, prostaglandins play a role in the regulation of both humoral and cell-mediated immunity, modulating cytokine and Ig production as well as T cell proliferation and activation. [6],[7],[8],[9],[10] For example, PGE2 enhances antibody production and promotes type 2 immune responses. PGE2 has been shown to directly promote Ig class switching in B cells acting through the EP2 and EP4 PGE2 receptors. [11] Recent findings showed that activated T and B cells express COX-2. Iniguez et al. demonstrated that basal low levels of COX-1 and COX-2 mRNAs can be detected in resting human T lymphocytes. COX-2 mRNA and protein expression were markedly increased after treatment with several stimuli mimicking TCR/CD3 T cell activation, COX-1 expression was not significantly affected by any of these treatments. [12] Ryan et al. demonstrated that COX-1 mRNA levels were constitutively expressed and remained unchanged during B cell activation. In contrast, Cox0 -2 mRNA was not detectable in unactivated B cells. However, activated human B cells strongly express COX-2 mRNA and protein, and produce PGs upon activation. Moreover, the NSAID (nonsteroidal anti-inflammatory drug ) indomethacin and COX-2-selective drugs profoundly inhibit the ability of human B cells to produce IgG and IgM. [10] It has been suggested that NSAIDs and COX-2 selective drugs might be used as immunosuppressive drugs and could have important applications in anti-inflammatory therapy. [10],[12]th

The reticulated crypt epithelium, also called lymphoepithelium, plays a key role in the initiation of immune responses in the palatine tonsils. In the crypts, luminal antigens are taken up by specialized cells of the reticulated epithelium. The cells form a specific intraepithelial micro-compartment that brings together high concentrations of foreign antigens, lymphocytes, and antigen-presenting cells such as macrophages and dendritic

cells. [13] The lymphoid cells found in the spaces of the reticulated crypt epithelium are mainly composed of B lymphocytes and T helper cells (CD4+). [14],[15] Approximately 50-90% of the intraepithelial lymphocytes are B cells. The majority of the B cells in the crypt epithelium are mature memory B cells with a high antigen presenting potential, permitting an early contact between antigen presenting B cells and T cells, and leading to a rapid secondary antibody response. [16],[17],[18]

Ruco et al. showed that intraepithelial lymphoid cells were a mixed cell population composed of 50% CD20-positive B lymphocytes, 40 % T lymphocytes with a 2.7 CD4/CD8 ratio, and 10% CD68-positive macrophages. [19]

Indeed, our findings were contributed to previous studies by immunohistochemically in tonsil tissue. [10],[11],[12],[20] In the present study, COX-1 and COX-2 positive cells were detected within the tonsils, primarily within the lymphocyte-rich crypt epithelium in paraffin embedded tissue. Most of these cells appeared to be small to medium-sized lymphocytes; some of them have plasmacytoid features. Given their location in the crypt surface, it seems likely that these cells are activated T and B cells. Hovever, other B and T cells in tonsil such as mantle zone and interfollicular area were not positive for COX-1 and COX-2 proteins. Probably, enzymes, in these cells may be undetectable levels by immunohistochemistry or antibody sensitivity may be not perfect. We observed that centrocyte and centroblast like cells that were activated B cells expressed COX-2, but not COX-1. Macrophages in germinal center showed COX-1 positivity. When B cells are activated, they differentiate into Ig-secreting plasma cells. We found that subepithelial cells, most of which were plasma cells have both COX-1 and COX-2 expression.

It is suggested that there is age-dependent altered proportion in subpopulations of tonsillar lymphocytes and the child's tonsil contains a greater concentration of lymphocytes than an adult's tonsil. [21],[22] We found that number of COX-1 and COX-2 positive cells was higher in children group than in adults, but it was not statistically significant. However, number of case with predominant plasma cells in subepitheial area was significantly high in adults.

We have shown expression of COX-1 and COX-2 in activated B and T cells in lymphoepithelium of patients with chronic tonsillitis. Further studies to identify the exact nature of cells that showed COX-1 and COX-2 expression in tonsil by double-staining method and explain to the pathogenic mechanism of adult or child with chronic tonsillitis, would be necessary. NSAIDs and selective COX-2 inhibitors will play important roles in the treatment of chronic tonsillitis. Additional studies are warranted to study the effects of these drugs in chronic tonsillitis.

   References Top

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11.Fedyk ER, Phipps RP. Prostaglandin E2 receptors of the EP2 and EP4 subtypes regulate activation and differentiation of mouse B lymphocytes to IgE-secreting cells. Proc Natl Acad Sci USA 1996;93:10978-83.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]  
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14.Harabuchi Y, Wakashima J, Murakata H, Yoshioka I, Yokoyama Y, Kataura A. Cytokine expression and production by tonsillar lymphocytes. Acta Otolaryngol Suppl (Stockh) 1996;523:75-7.  Back to cited text no. 14      
15.Tang X, Hori S, Osamura RY, Tsutsumi Y. Reticular crypt epithelium and intra-epithelial lymphoid cells in the hyperplastic human palatine tonsil: an immunohistochemical analysis. Pathol Int 1995;45:34-44.  Back to cited text no. 15  [PUBMED]    
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19.Ruco LP, Uccini S, Stoppacciaro A, Pilozzi E, Morrone S, Gallo A, et al. The lymphoepithelial organization of the tonsil: An immunohistochemical study in chronic recurrent tonsillitis. J Pathol 1995;176:391-8.  Back to cited text no. 19  [PUBMED]    
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Correspondence Address:
Fatma Husniye Dilek
PK: 70 03100 Afyonkarahisar
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.68272

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