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Published on: August 16, 2021
[Effect of interleukin-17 on neutrophil apoptosis in patients with tuberculosis]
Lina Jiang1, Chunyan Yao2, Qili Jin2
1Department of Pathophysiology, Anhui Key Laboratory of Infection and Immunity; Bengbu 233030, China.
Objective:
To investigate the effect of interleukin (IL)-17 on the apoptosis of neutrophils (PMNs) from peripheral blood of patients with pulmonary tuberculosis (TB) and explore the possible involved signaling pathway.
Methods:
The fresh isolated PMNs from peripheral blood of TB patients and healthy adults were cultured for 0-24 hours, and then stained with annexin V. The flow cytometry was used to measure cell apoptosis of PMNs. The fresh isolated PMNs were cultured with different concentrations of IL-17 for 24 hours, with or without pretreatment of MAPK inhibitor U0126 for 30 minutes, the apoptosis of PMNs was detected by flow cytometry.
Results:
The apoptosis of PMNs in both TB patients and healthy adults increased with the culture time going on (P<0.05). The spontaneous apoptotic (annexin V⁺) rates of PMNs at 0, 6, 12 and 24 hours of culture time in TB patients were (4.49 ± 1.39)%, (21.89 ± 2.90)%, (39.96 ± 4.15)%, and (68.35 ± 7 .01)%, respectively, which were significantly higher than the corresponding ones in normal healthy groups, (2.65 ± 0.75)%, (11.00 ± 1.72)%, (25.84 ± 3.90)%, and (45.59 ± 4.10)%, respectively (P<0.05). After cultured with IL-17 for 24 hours, the apoptotic rates of PMNs in TB patients and healthy adults were respectively (59.81 ± 7.19)% and (34.65 ± 4.79)% in the group of IL-17 at 0.5 μg/L, and (51.62 ± 6.91)% and (29.04 ± 3.62)% in the group of IL-17 at 5 μg/L; they were significantly lower than those in control groups without IL-17, (68.35 ± 7.01)% and (45.59 ± 4.10)%, respectively, (P<0.05). However, in the group of IL-17 at 50 μg/L, the apoptosis rates of PMNs in TB patients and healthy adults were (76.04 ± 5.59)% and (53.24 ± 4.62)%, respectively, which were obviously higher than those of the control groups without IL-17 (P<0.05). Pretreatment of PMNs with U0126 mostly inhibited the anti-apoptosis effect of IL-17 at 5 μg/L on PMNs of TB patients and normal subjects.
Conclusion:
The apoptosis of PMNs in both TB patients and healthy adults increases along with the culture time, and the apoptosis rate of PMNs in TB patients is higher than that of healthy adults. The lower concentrations of IL-17 can delay, but the higher concentration of Il-17 can accelerate the apoptosis of PMNs in TB patients. The inhibitory role of IL-17 in apoptosis of PMNs may be involved in the ERK pathway.
Insights
Neutrophil apoptosis increases with culture time, and is higher in tuberculosis patients. Interleukin-17 (IL-17) at low doses delays neutrophil apoptosis, while high doses accelerate it, potentially via the ERK pathway.
Area of Science:
- Immunology
- Cell Biology
Context:
- Pulmonary tuberculosis (TB) is a significant global health challenge.
- Neutrophils play a critical role in the immune response to TB.
- Dysregulation of neutrophil apoptosis may contribute to TB pathogenesis.
Purpose:
- To investigate the effect of interleukin-17 (IL-17) on neutrophil apoptosis in TB patients.
- To explore the signaling pathway involved in IL-17-mediated neutrophil apoptosis.
Summary:
- Neutrophil apoptosis rates increased with culture time and were higher in TB patients compared to healthy adults.
- Low concentrations of IL-17 delayed neutrophil apoptosis, while high concentrations accelerated it in both groups.
- The anti-apoptotic effect of IL-17 was partially inhibited by a MAPK pathway inhibitor (U0126), suggesting involvement of the ERK pathway.
Impact:
- This study elucidates the complex role of IL-17 in neutrophil apoptosis during TB.
- Findings may offer insights into novel therapeutic strategies targeting neutrophil apoptosis in TB management.
- Understanding IL-17's influence on neutrophils could improve TB treatment outcomes.
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