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. 2023 Apr 15;18(1):20220588.
doi: 10.1515/biol-2022-0588. eCollection 2023.

Interaction between the PI3K/AKT pathway and mitochondrial autophagy in macrophages and the leukocyte count in rats with LPS-induced pulmonary infection

Chao Wu  1 , Lianghua Guo  2 , Xirennayi Muhataer  1 , Qifeng Li  3 , Zhichuang Lian  1 , Yafang Li  1 , Wenyi Wang  1 , Wei Ding  1 , Yuan Zhou  1 , Xiaohong Yang  1 , Muzhi Chen  4
Affiliations

Interaction between the PI3K/AKT pathway and mitochondrial autophagy in macrophages and the leukocyte count in rats with LPS-induced pulmonary infection

Chao Wu et al. Open Life Sci. .

Abstract

This study examined the effects of the PI3K/AKT pathway and mitochondrial autophagy in macrophages and the leukocyte count after pulmonary infection. Sprague‒Dawley rats were subjected to tracheal injection of lipopolysaccharide (LPS) to establish animal models of pulmonary infection. By inhibiting the PI3K/AKT pathway or inhibiting/inducing mitochondrial autophagy in macrophages, the severity of the pulmonary infection and the leukocyte count were altered. The PI3K/AKT inhibition group did not show a significant difference in leukocyte counts compared with the infection model group. Mitochondrial autophagy induction alleviated the pulmonary inflammatory response. The infection model group had significantly higher levels of LC3B, Beclin1, and p-mTOR than the control group. The AKT2 inhibitor group exhibited significantly increased levels of LC3B and Beclin1 compared with the control group (P < 0.05), and the Beclin1 level was significantly higher than that in the infection model group (P < 0.05). Compared with the infection model group, the mitochondrial autophagy inhibitor group exhibited significantly decreased levels of p-AKT2 and p-mTOR, whereas the levels of these proteins were significantly increased in the mitochondrial autophagy inducer group (P < 0.05). PI3K/AKT inhibition promoted mitochondrial autophagy in macrophages. Mitochondrial autophagy induction activated the downstream gene mTOR of the PI3K/AKT pathway, alleviated pulmonary inflammatory reactions, and decreased leukocyte counts.

Keywords: PI3K-AKT-mTOR pathway; leukocyte; mitochondrial autophagy; molecule; severe pneumonia.

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Conflict of interest statement

Conflict of interest: Authors state no conflict of interest.

Figures

Figure 1
Figure 1
Hematoxylin–eosin staining outcomes of the pulmonary tissue in the different groups (n = 3). The black arrow indicates normal alveolus, the green arrow indicates inflammatory cell infiltration, the blue arrow indicates inflammatory exudation, and the red arrow indicates alveolar septal edema.
Figure 2
Figure 2
Hematoxylin–eosin staining scores of the pulmonary tissue in different groups (n = 3). One-way analysis of variance is used for comparison among groups. △P < 0.05, vs the control group; ▲P < 0.05, vs the infection model group; ▽P < 0.05, vs the AKT2 inhibitor group; and ▼P < 0.05, vs the mitochondrial autophagy inhibitor group.
Figure 3
Figure 3
Protein levels in peripheral CD14+ monocyte/macrophages in the different rat groups. Each group contains three animals, and flow cytometry is used for western blot analysis of CD14+ CELLS, with three repetitions in each group. One-way analysis of variance is used for comparison among groups. A, Splicing band diagram of the target proteins. B, The levels of different proteins in macrophages. B1-5, The levels of the key proteins in the PI3K/AKT pathway. B6-7, Markers of mitochondrial autophagy in macrophages. △P < 0.05, vs the control group; ▲P < 0.05, vs the infection model group; ▽P < 0.05, vs the AKT2 inhibitor group; and ▼P < 0.05, vs the mitochondrial autophagy inhibitor group.
See this image and copyright information in PMC

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