Sp-A and Tlr4 Localization in Lung Tissue of Sm-Exposed Patients Publisher Pubmed



Ghaffarpour S¹ ; Foroutan A² ; Askari N³ ; Abbas FM⁴ ; Salehi E⁵ ; Nikoonejad M¹ ; Naghizadeh MM^{1, 6} ; Eskandarian M⁷ ; Moghadam KG⁸ ; Akbari HMH^{9, 12} ; Yarmohammadi ME¹⁰ ; Ghazanfari T^{1, 11}
Source: International Immunopharmacology Published:2020

Abstract

Introduction: Long-term pulmonary complications are one of the major long-term consequences of sulfur mustard (SM) exposure. Toll-like receptor 4 (TLR4) involves in the pathogenesis of several pulmonary disorders. Surfactant protein-A (SP-A) regulates LPS-induced TLR4 localization and activation responses. However, the intensity and significance of TLR4 and SP-A expression by lung cells in SM-exposed patients is not clear. Methods: The gene expression of TLR4 (through real-time PCR) and TLR4 and SP-A positive cells and alveolar type II cells, as SP-A producers, (using IHC) were assessed in formalin fixed paraffin embedded (FFPE) specimens from SM-exposed (n = 17), and non-SM exposed individuals (n = 12). Results: TLR4 gene expression did not change between study groups. However, its cell surface presentation was significantly reduced in SM-exposed patients and particularly in which with constrictive bronchiolitis compared with the control group (P < 0.001 and P = 0.002, respectively). Frequency of alveolar type II cells was lower in the case group rather than the control group while the number of SP-A positive cells did not alter. Conclusions: These findings suggest that reduced TLR4 cell surface presentation may have anti-inflammatory function and SP-A may have a critical role in regulation of inflammatory responses in SM-exposed patients. Further investigation on other possible mechanisms involved in TLR4 internalization maybe help to illustrate the modulatory or inflammatory activity of TLR4 in these patients. © 2019