TILRR Promotes Migration of Immune Cells Through Induction of Soluble Inflammatory Mediators

Mohammad Abul Kashem; Xiaoou Ren; Hongzhao Li; Binhua Liang; Lin Li; Francis Lin; Francis A Plummer; Ma Luo

doi:10.3389/fcell.2020.00563

TILRR Promotes Migration of Immune Cells Through Induction of Soluble Inflammatory Mediators

Front Cell Dev Biol. 2020 Jul 3:8:563. doi: 10.3389/fcell.2020.00563. eCollection 2020.

Authors

Mohammad Abul Kashem^{1

2

3

4}, Xiaoou Ren^{5

6}, Hongzhao Li^{1

4}, Binhua Liang^{2

4

7}, Lin Li^{2

4}, Francis Lin^{5

6

8}, Francis A Plummer¹, Ma Luo^{1

2

4}

Affiliations

¹ Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada.
² JC Wilt Infectious Diseases Research Centre, Winnipeg, MB, Canada.
³ Department of Microbiology and Veterinary Public Health, Chittagong Veterinary and Animal Sciences University, Chittagong, Bangladesh.
⁴ National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada.
⁵ Department of Biosystems Engineering, University of Manitoba, Winnipeg, MB, Canada.
⁶ Department of Physics and Astronomy, University of Manitoba, Winnipeg, MB, Canada.
⁷ Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada.
⁸ Department of Immunology, University of Manitoba, Winnipeg, MB, Canada.

Abstract

TILRR has been identified as an important modulator of inflammatory responses. It is associated with NF-κB activation, and inflammation. Our previous study showed that TILRR significantly increased the expression of many innate immune responsive genes and increased the production of several pro-inflammatory cytokines/chemokines by cervical epithelial cells. In this study, we evaluated the effect of TILRR-induced pro-inflammatory cytokines/chemokines on the migration of immune cells. The effect of culture supernatants of TILRR-overexpressed cervical epithelial cells on the migration of THP-1 monocytes and MOLT-4 T-lymphocytes was evaluated using Transwell assay and a novel microfluidic device. We showed that the culture supernatants of TILRR-overexpressed HeLa cells attracted significantly more THP-1 cells (11-40%, p = 0.0004-0.0373) and MOLT-4 cells (14-17%, p = 0.0010-0.0225) than that of controls. The microfluidic device-recorded image analysis showed that significantly higher amount with longer mean cell migration distance of THP-1 (p < 0.0001-0.0180) and MOLT-4 (p < 0.0001-0.0025) cells was observed toward the supernatants of TILRR-overexpressed cervical epithelial cells compared to that of the controls. Thus, the cytokines/chemokines secreted by the TILRR-overexpressed cervical epithelial cells attracted immune cells, such as monocytes and T cells, and may potentially influence immune cell infiltration in tissues.

Keywords: MOLT-4; THP-1; TILRR; Transwell assay; cervical epithelial cell culture supernatants; microfluidic device; pro-inflammatory cytokines/chemokines.