Disertasi

Dampak Polusi terhadap Sawar Epitel, Inflamasi, dan Pemulihan Epitel Rinitis Alergi: Kajian terhadap Protein Tight Junction, Thymic Stromal Lymphopoietin, Aryl Hydrocarbon Receptor, Interleukin-4, dan Transient Receptor Potential Vanilloid-1 = Pollution Impact on Epithelial Barrier, Inflammation and Epithelial Repair in Allergic Rhinitis: Analysis of Tight Junction Proteins, Thymic Stromal Lymphopoietin, Aryl Hydrocarbon Receptor, Interleukin-4 and Transient Receptor Potential Vanilloid-1.

Rinitis alergi (RA) merupakan masalah kesehatan global yang mengakibatkan gangguan kualitas hidup. Prevalensi RA terus meningkat seiring memburuknya kualitas udara. Sampai saat ini, masih ada sekitar 20% penderita RA yang tidak membaik dengan terapi optimal dan ini dikaitkan dengan polusi udara yang belum bisa diatasi. Masih diperlukan bukti ilmiah yang mendukung mekanisme gangguan integritas epitel mukosa hidung dan keparahan kondisi RA akibat polusi udara. Penelitian ini bertujuan memperlihatkan dampak polusi terhadap RA, khususnya integritas epitel mukosa hidung serta pemulihannya. Penelitian ini terdiri dari 2 studi. Studi in vitro eksperimental membandingkan antara kultur primer HNEC (human nasal epithelial cell) RA persisten terpajan diesel exhaust particle (DEP) 40 g/mL dan alergen Dermatophagoides pteronyssinus (Der pt) 20 g/mL dengan kultur kontrol yang mendapatkan Der pt 20 g/mL. Pajanan diberikan selama 3 hari, dilanjutkan pembilasan DEP dua kali dengan interval 24 jam, yang dilanjutkan dengan observasi 72 jam. Ekspresi zonula occludens (ZO)-1 dan claudin-1 diperiksa dengan metode imunofluoresensi di HNEC pada waktu yang telah ditentukan, disertai pengukuran kadar TSLP dalam medium kultur. Studi in vivo merupakan studi potong lintang komparatif membandingkan pasien RA persisten wilayah polusi tinggi Jakarta dan polusi rendah Ciawi. Ekspresi ZO-1 dan claudin- 1 dari jaringan biopsi konka inferior diperiksa dengan imunohistokimia, sedangkan kadar AhR, IL-4, dan TRPV-1 dari kerokan mukosa diperoleh melalui ELISA. Ekspresi ZO-1 dan claudin-1 ditemukan lebih rendah, baik di kultur terpajan DEP maupun di kelompok RA wilayah polusi tinggi (p < 0,05 untuk claudin-1). Kedua studi memperlihatkan translokasi claudin-1 ke sitoplasma dan lapisan basal. Respons inflamasi AhR, IL-4 dan TRPV-1 ditemukan lebih tinggi di kelompok RA wilayah polusi tinggi (p < 0,05), sedangkan TSLP tidak ditemukan meningkat pada kultur terpajan DEP. Ditemukan peningkatan ekspresi ZO-1 dan claudin- 1 pasca pembilasan DEP (p < 0,05 untuk claudin-1), sedangkan kadar TSLP menurun bermakna pada akhir observasi setelah pembilasan kedua. Polusi menyebabkan gangguan sawar epitel mukosa dan peningkatan respons inflamasi melalui mekanisme persinyalan AhR, yang diikuti dengan peningkatan IL-4 dan TRPV-1. Modulasi respons inflamasi melalui sinyal TSLP bergantung pada derajat pajanan polutan. Pemulihan epitel dapat terjadi setelah eliminasi polutan walaupun tidak optimal.
Kata kunci: Epitel mukosa hidung, inflamasi, polusi, rinitis alergi, tight junction


Allergic rhinitis (AR) is a global health problem that impairs patient’s quality of life. The prevalence of AR is projected to increase as air quality deteriorates. Approximately 20% of AR patients experience persistent symptoms despite optimal treatment, which is strongly associated with unresolved air pollution. Further studies are needed to support the mechanism by which air pollution disturb nasal epithelial integrity and exacerbate AR symptoms. This study aims to demonstrate the impact of air pollution to AR, focusing on the nasal epithelial barrier and its recovery process. The methodology involved in vitro and in vivo studies. The experimental in vitro study compared primary cultures of human nasal epithelial cells (HNEC) from patients with persistent AR. One group was exposed to 40 µg/mL diesel exhaust particle (DEP) and 20 µg/mL Dermatophagoides pteronyssinus (Der pt), while another was exposed to only 20 µg/mL of Der pt as control. The exposure phase lasted three days, followed by two DEP rinses at 24- hour intervals and a subsequent observation period of up to 72 hours. ZO-1 and claudin-1 expression in HNEC were assessed using immunofluorescence, while TSLP levels measured from culture medium. The in vivo comparative crosssectional study compared persistent allergic rhinitis patients residing in Jakarta, a high-pollution region, with those in Ciawi, a low-pollution region. ZO-1 and claudin-1 expression from inferior turbinate biopsy were assessed using immunohistochemistry, while AhR, IL-4, and TRPV-1 levels measured from mucosal scraping. Both DEP exposed culture and patients in high-pollution region showed lower expression of ZO-1 and claudin-1 (p < 0.05 for claudin-1). This reduction was accompanied by translocation of claudin-1 to the cytoplasm and basal layer in both studies. Inflammatory markers AhR, TRPV-1, and IL-4 were elevated in the high-pollution patient group (p < 0.05), while TSLP did not increase in the DEP-exposed cultures. A recovery trend was observed post DEP-rinsing, as ZO-1 and claudin-1 expression increased (p < 0.05 for claudin-1) and TSLP levels significantly declined after the second rinse. Pollution impairs nasal epithelial barrier and heightens inflammatory responses via AhR signaling pathway, which induced TRPV-1 and IL-4 elevation. Modulation of inflammatory response through TSLP signaling pathways depends on the pollutant concentration. Elimination of pollutant exposure showed nasal epithelial repair although not fully restored.
Keywords: allergic rhinitis, inflammation, nasal epithelium, pollution, tight junction