C5a Induces Inflammatory Signaling and Apoptosis in PC12 Cells through C5aR-Dependent Signaling: A Potential Mechanism for Adrenal Damage in Sepsis
Abstract
:1. Introduction
1.1. Sepsis
1.2. The Complement System
1.3. Complement C5a
1.4. Primary Adrenal Dysfunction
1.5. Research Objectives and Hypothesis
2. Results
2.1. Complement C5a Induces Caspase Activation and Apoptosis in PC12 Cells
2.2. PMX-53 Inhibits C5a-Induced Caspase Upregulation
2.3. C5a Induces Inflammatory Signaling in PC12 Cells
2.4. Complement C5a Induces Protein Kinase Signaling in PC12 Cells
3. Discussion
3.1. C5a and Apoptosis
3.2. C5a and Cellular Signaling
3.2.1. JNK
3.2.2. ERK
3.2.3. p38
3.2.4. AKT
3.2.5. Intercellular and Inflammatory Signaling
3.2.6. Chemotaxis
3.3. Clinical Relevance and Future Directions
4. Materials and Methods
4.1. Materials
4.2. Cell Culture
4.3. C5a Treatment
4.4. Caspase Activation and Cell Death Assay
4.5. Antibody Array
4.6. Phosphorylation ELISA
4.7. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A
References
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Protein | Percentage Change | SEM (%) | Significant (p < 0.05) | Function |
---|---|---|---|---|
Activin A | 17.59 | 4.868 | Yes | Cell Cycle Progression, Cell Proliferation, and Apoptosis [47] |
FAS | 91.74 | 23.7 | Yes | Induction of Apoptosis [48] |
FASL | 99.56 | 50.96 | Yes | |
GALECTIN 1 | 39.95 | 11.54 | Yes | Regulation of Cell Cycle [49] |
IL-1α | 22.68 | 4.439 | Yes | Alarmin and Inflammatory Process [50] |
IL-3 | 17.01 | 1.369 | Yes | Inflammatory processes, Cell Growth, and Differentiation [51] |
IL-4 | 29.42 | 5.13 | Yes | Proliferation and Cell Survival [52] |
IL-7 | 61.77 | 19.08 | Yes | Proliferation and Cell Survival [53] |
MIP-1a | 54.91 | 12.89 | Yes | Immune Cell Activation and Chemotaxis [54] |
PDGF-BB | 88.81 | 20.92 | Yes | Proliferation, Immune Cell Activation, and Differentiation [55] |
Protein | Percentage Change | SEM (%) | Significant (p < 0.05) | Function |
---|---|---|---|---|
CCL20 | −6.356 | 1.787 | Yes | Immune Migration and Chemotaxis [56] |
CINC1 | −22.5 | 6.018 | Yes | Neutrophil Chemoattractant [57] |
CINC2 | −22.68 | 4.599 | Yes | Immune Cell Recruitment and Chemotaxis [58] |
ICAM-1 | −14.18 | 3.261 | Yes | Cell Adhesion and Immune Cell Recruitment [59] |
IL-13 | −12.33 | 2.959 | Yes | Anti-inflammatory Effects [60] |
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Mrozewski, L.; Tharmalingam, S.; Michael, P.; Kumar, A.; Tai, T.C. C5a Induces Inflammatory Signaling and Apoptosis in PC12 Cells through C5aR-Dependent Signaling: A Potential Mechanism for Adrenal Damage in Sepsis. Int. J. Mol. Sci. 2024, 25, 10673. https://doi.org/10.3390/ijms251910673
Mrozewski L, Tharmalingam S, Michael P, Kumar A, Tai TC. C5a Induces Inflammatory Signaling and Apoptosis in PC12 Cells through C5aR-Dependent Signaling: A Potential Mechanism for Adrenal Damage in Sepsis. International Journal of Molecular Sciences. 2024; 25(19):10673. https://doi.org/10.3390/ijms251910673
Chicago/Turabian StyleMrozewski, Lucas, Sujeenthar Tharmalingam, Paul Michael, Aseem Kumar, and T. C. Tai. 2024. "C5a Induces Inflammatory Signaling and Apoptosis in PC12 Cells through C5aR-Dependent Signaling: A Potential Mechanism for Adrenal Damage in Sepsis" International Journal of Molecular Sciences 25, no. 19: 10673. https://doi.org/10.3390/ijms251910673